A close second would have to be Alam/Aramu who is an ordinary German Shepherd by breed but is missing both his ears as well as the skin on his muzzle, resulting in a rather terrifying look. The trope gets subverted when he has a Heel-Face Turn, though.
Ralph Werec in Soukou No Strain is a creepy albino with a scar across his eye, which turns pink when he's angry. However, when he was sane, his skin was less pale, his hair was blond and more meticulously hair-gelled, and he didn't have the scar.
The Noah look normal in human form. In Noah form, they have a line of cross-shaped marks across their foreheads.
While only Allen can see it, all Akuma are powered by a bound human soul protruding from their bodies.
Played with with Allen, whose left arm is twisted and red, with a big cross on the back of his hand and occasionally a will of its own. His parents abandoned him because it was so freaky. Not only is he a wonderful person, the scary arm is actually a holy weapon for destroying Akuma. His other 'mark' is his funny-looking cursed right eye, which is a mark of sin but also one of his messianic attributes, since it causes him suffering and keeps him from ever forgetting there are innocent souls within the Akuma who he wants to save.
As well as Ed's entire right arm, though he's the series hero and isn't evil at all. It does show, however that he committed what many believe to be one of the greatest sins in attempting human transmutation. Playing God and all.
When not wearing his gloves, Gendo Ikari from Neon Genesis Evangelion has what looks like a fetus fused unto his hand. He has his reasons...
Haji of Blood+ is a subversion. Although he is the only chiropteran to have a permanent, visible indication of his inhuman nature - a literal red right hand with monstrous claws - he is unequivocally a good guy, and the only chevalier in the series who never fully transforms into a monstrous chiropteran combat form, instead limiting himself to transforming his other hand and growing batlike wings.
The evil Nazi Doctor known only as the Doctor who has a sixth finger. However, it's not very noticeable unless you pay much attention to his hands.
Played with when Seras gains her shadow-arm.
Zorin Blitz's right eye is almost completely black and in a permanent squint, while the other is bright green and is able to move around normally.
The Anime has Incognito, a cone-headed vampire with a massive left eye.
The left hand of the titular character of Hell Teacher Nube is actually a sealed Oni, Baki, which replaces the left hand he lost fighting said Oni. Most of the time, it looks like his regular hand wearing a black leather glove; when his students are threatened by spectral horrors, he will reveal it as a monstrously large, dark red hand with visible tendons and black claws. However, he constantly seeks a way to seal it permanently, as only the influence of his childhood teacher prevents the Oni from taking over his entire body.
Most of the villains have something of the sort, even if they don't start as demons. Father Mozgus, for example, has an unnaturally flat face (revealed to be the result of him slamming his face into the ground two hundred times every day during his daily prayers). Guts, having a touch of Genre Savvy, sometimes marks his enemies by looking for this sort of trait.
The Godhand, the Big Bad Duumvirate of Berserk, is a very literal case. The podium that they present themselves to would-be sacrifices from is a red right hand. Genius, you say?
Towa Kannagi from Mermaid Saga is a white haired girl that always keeps her right hand heavily bandaged. What's under there isn't so much a hand as it is a mottled, pulsating claw she received after drinking mermaid's blood. The constant physical pain it leaves her in (not to mention her forced isolation because of it) has left her more than a little deranged.
InuYasha has Naraku, whose incarnations are marked by a spider-shaped scar on the back.
Ryo Takatsuki of Project ARMS has a literal Red Right Hand, which is a nanite-based AI prosthetic known as the Jabberwock. Like that's gonna work out well. When the hand starts spreading over the rest of the body, run...now.
In Darker than Black, it's fairly obvious that we shouldn't trust Wei or Maki, even though a big deal isn't made about it. More explicitly, the Red Eyes, Take Warning effect that accompanies a contractor using their powers is definitely a bad sign. More literally, the leader of The Syndicate turns out to have two prosthetic hands.
In case the red glowing eyes of a contractor weren't enough of a hint that it's about to hit the fan, they also emit synchrotron radiation when activating their powers. This is not something that normal humans are supposed to do.
A villain with a literal Red Right Hand is Devimon, the first Big Bad of Digimon Adventure. It's far from the only characteristic that identifies him as evil.
You Higuri's manga Cantarella features a possessed Cesare Borgia with a color-vague demonic arm, which eventually had to be lopped off to stop him from becoming an avatar of Satan. Mind you, while the explanation is textbook Red Right Hand, the arm subplot seems to have been included entirely so that Cesare's faithful servant had an excuse to tie him to the bed.
Some of the less thinky Detective Conan episodes use this trope to show who amongst them is the killer, like the sinister looking head librarian who exudes 'evil boss' vibes from the moment he appears on-screen in the book drug trafficking episode.
Sora, in an arc of Shippuden, has a demonic-looking right hand. He wasn't necessarily evil, just a Jerkasswho also happens to be a vessel for some of the Nine-Tailed Fox's chakra that has been cultivated and injected into Sora by the real villain.
When Naruto tries to defeat the Kyuubi on his own, he has his former inner hatred shoved into his face, and then Naruto's left eye transforms into that of his inner evil counterpart. On the outside, he develops a 2-tailed fox cloak on the right side and a 2-tailed V2 cloak on his left. note It would have gone further if his mother didn't intervene.
The titular Vampire Hunter D has a peculiar left hand. Embedded into his left palm is a parasitic, sentient face capable of holding conversations with D: mostly about not holding up the image of a vampire. It rather accentuates D's angst: half human, half vampire, yet not really comfortable with either race. Beyond the snark, though, it has a few minor capabilities of its own and will show genuine concern if D gets in real trouble.
Middle-level Mazoku (demons) from the Slayers universe sometimes try to take human form, but it is always... off. Take Kanzel and Mazenda from NEXT: the former has unnatural skin and hair color, and the latter is ludicrously ignorant of human fashion, appearing to wear a glaringly anachronistic outfit.Mazoku Generals, Priests and Lords, however, are powerful enough to pull off a perfect imitation of human form.
Ciel Phantomhive of Black Butler wears an eyepatch to obscure the fact his right eye is a pale purple color and has a pentagram etched into it; this is the physical representation of his pact with Sebastian. Making things worse is that it lights up when he's giving Sebastian a direct order.
All Puella Magi have a colored emblem on their middle fingernail.
While Hellboy is a red-skinned, twin-horned demon to begin with, he's actually fairly human-looking and easy on the eyes for the most part. With, of course, the notable exception of (yes) his right hand and forearm, which are thrice as big as his human-standard left, only has three fingers and a thumb, and is made entirely of a demonic, totally indestructible mineral, which raises the question of where the eldritch symbols carved into it came from. It's eventually revealed that the stone arm is the literal key to immense demonic power and is somehow the means by which Hellboy is prophesized to trigger the apocalypse.
Satan as portrayed in The Sandman had an aura of Grecian beauty, but his hair kept forming little horn-shapes. His resemblance to David Bowie upped the creepiness level yet further. Also the nightmare called The Corinthian, who hid his eyes opaque sunglasses because instead of eyes he had two tiny mouths with actual teeth, which he used to eat the eyes of his victims to learn anything they had seen. The Corinthian gains normal eyes after he was temporarily made mortal and developed compassion for others, however.
Herr Starr, the Big Bad of Garth Ennis' Preacher, starts with a nonfunctional right eye and five scar lines around it. As the series goes on, the "redness" only increases: He gets his left ear shot off, a nasty (and phallic) line is cut into his scalp, he loses his right lower leg to cannibals and his penis gets bitten off by a dog. Crosses the Line Twice when he says "My cock is in the bitch's mouth. And not in a good way."
Batman's rogue's gallery has three big examples of this. The Joker is often depicted with a permanent freaky grin on his chalk white face, The Penguin has a distinctly birdlike appearance (sometimes including flippers for hands), and Two-Face has half of his face horribly scarred by acid.
Another example is Killer Croc, and he becomes more and more of an example as time goes on. When he first appeared, he looked like a normal person, save for green scales covering his body. The official story is that he has a bizarre version of atavism, which gets worse as time goes on, making him look more and more reptilian. Things eventually got better for Croc when he learned that he was very slowly turning into an actual crocodile - mentally as well as physically - and found himself welcomed by Swamp Thing to live as a reptile in the Louisiana swamps. There he would be able to live among his own kind - and if people still did make fun of him for his appearance, over time he'd become too mindless to care. But it is doubtful that Croc's Heel-Face Turn was permanent, or if he never decided to return to Gotham City.
The French comic book Le vagabond des limbes once featured this - Axle, the hero, spends most of the series looking for Chimeer, a mysterious woman that is obviously in love with him, and upon failure to have God himself locate her Axle puts him to the task of creating her. The resulting bloody pile of randomly fused red flesh seems to be the source of the hero's truly memorable horrified stare... but no! There is the unmistakable arm and voice of Chimeer coming out of it, and her arm is the only thing not red and horrible! This is obviously a subversion as the newly created "Chimeer" is genuinely in love with Axle and only means well...
Superman: Yes, Lex Luthor, yes, mechanical right hand. Ironically enough, from his kryponite ring (of hate). Also, Bald of Evil.
In X-Men Reverend Stryker finds the remains of a Sentinel from the future and uses the robot's glowing PINK hand as a glove and an apparent weapon. He dies before he gets to use it. Just goes to show you need to get a real red hand. No one respects you with a pink one.
DC Comics' Heroic Fantasy hero Claw the Unconquered had a literal demonic hand, hidden under a red glove to reduced its evil influence on him.
Dr. Doom, whose face is so horribly scarred that it's never shown. According to Reed Richards, the scar on his face was only slightly superficial. But Von Doom's ego was so great, that even the slightest imperfection was enough to vow vengeance on Richards. Later, upon receiving his armor from Tibetan mystics, he didn't even wait until the metal had cooled before trying on the mask, which is the true cause of his now hideous deformity.
Conan the Barbarian: Conan's ally Fafnir Hellhand twice lost his arm, and twice had it replaced with a demonic substitute that had a will of its own.
Watchmen: Former stage magician turned criminal mastermind Moloch has pointed, satanic ears. He resembles Orlok.
Hideaki's right hand man from Silent Dragon has a pair of cybernetic arms that are designed to look reptilian and dragonlike.
Captain Semtin has obvious, creepy prosthetic eyeballs and mechanical thingies in his ears. He abandons some of his soldiers on Ryloth, which has local rules that offworlders with no influence or transportation get sold into slavery. The soldiers promptly switch sides.
A prominent character in the Hellblazer series (particularly in the trade paperback, "The Red Right Hand") develops a literal red right hand (occasionally drawn as his left hand) after murdering his girlfriend and recklessly causing the terrible demise of several innocent people, including children, infants, and young parents. The hand becomes redder and darker in accordance with changes to his character as the story progresses.
New Mutants member Josh Foley aka Elixir was a golden skinned mutant whose Omega-level power over biology granted him incredible healing abilities. When he used those powers to kill a villain who orchestrated his girlfriend's assassination his skin turned black and he entered a catatonic state. He got better eventually, but ever since his golden skin is marred by a splotch of darkness that keeps moving around his body — a permanent reminder that he killed someone and that he can kill again.
In CrossGen comic Sojourn, Mordath's evil nature warped the Sigil he received, so instead of a red-and-yellow yin-yang symbol it was entirely red. Receiving the Sigil in the first place brought him Back from the Dead, so he's also a zombie.
Justified example in Creature Tech. Jameson exchanged his hand for that of the demon Hellcat so he could gain demonic powers, and to prevent his soul from being taken to Hell when he died. When Dr. Ong cuts off Jameson's hand, the demons of Hell show up for Jameson's soul.
Witches in the afterlife of Resonance Days look mostly human, but retain traits of their original form. Most of the time, it's a fairly minimal detail - Arzt has syringes instead of fingers, Nie has a heart tattoo on her chest, Charlotte has a monkeylike tail. Others, however, head more into Cute Monster Girl territory, most famously Oktavia, who retains her witch form's lower body.
Films — Animated
In Coraline, everyone in the Other World appears to be more attractive than their real-world counterparts with the exception of those goddamn button eyes.
In Mulan, the Huns have gray skin and yellow eyes.
The Lion King: Scar is the only lion in the pride with a different color scheme and to have his claws bared all the time, and of course, he has a scar over one eye. Also, in the German version of "Be Prepared", he sings "Meine Zähne sind blank wie mein Neid", which translates as "My teeth are uncovered like my envy".
Subverted with the protagonist Kovu (who has more or less the same color scheme as Scar, and even acquires a scar over his eye about halfway through the movie).
Played it straight with the other outsiders, most notably Zira (who has a vertical stripe on her head and an Ear Notch). Before the end battle, the outsider lionesses all walk through mud, just so we (and maybe they themselves) can tell them apart from their prideland counterparts in the heat of the battle. By the time they realize there's really not all that much of a difference between the two groups, and reunite, they're all clean again, though their distinguishing drawing style remains.
In Toy Story 3, the Baby's lazy eye is an early indicator that it and the daycare as a whole are not as wholesome as they appear to be.
GoldenEye: Janus take his name from the burns that cover half is face.
The World Is Not Enough: Renard has a scar on his forehead from a bullet's entry wound. Renard's accomplice, Elektra, has a mutilated earlobe which she hides behind a large earring.
Zao from Die Another Day has diamonds seared to his face. More pointedly, his skin is bleached and his hair has fallen out as a side effect of incomplete gene therapy. Gustav Graves is an insomniac. He must spend one hour per day in an REM device to avoid going mad.
Casino Royale: Le Chiffre's eye weeps blood. In the opening of said film, Bond chases down a bombmaker (Mollaka) with chemical burns on the right side of his head.
Skyfall: Silva wears a prosthetic to hide the massive cavity inside his head, a result of part of his skull being rotted away by a defective cyanide capsule. This is semi-deconstructed by the fact that he only incurred such injury due to his willingness to die for M when he was still an MI6 agent himself, and Not So Different from Bond.
Azrael, the secondary villain in Dogma, has little tiny horns. Though this is less a physical defect and more that he's literally a demon.
In the movie Mystery Men, Casanova Frankenstein has creepy fingernails.
The pimp in Taxi Driver has long fingernails, apparently for cocaine.
Kevin the cannibal, from Sin City, had claws. And then there's Yellow Bastard, which should be pretty self-explanatory.
The six-fingered Count Rugen from The Princess Bride, as well as his albino assistant. In the book, though not the film, Vizzini is a hunchback as well.
Doctor Strangelove: His right hand tried to strangle him and would compulsively do a Nazi salute. Unusually for this trope this is played entirely for comedy.
Torgo's knees in "Manos" The Hands of Fate. They were supposed to make him look like a Satyr, which is more often lost on people who have only watched the MST 3 K version, which frequently cuts off his "hooves."
In the X-Men movies, Mystique can look like anybody she feels like, but she can't cover up the scars Wolverine gave her in the first movie. Also, her eyes occasionally flash yellow. This is contrary to the comics, where she has total control over her physical appearance, but Wolverine can still identify her because she can't mask her scent.
In John Carpenter's In the Mouth of Madness (1995), readers of the books of hack horror writer Sutter Cane go insane and develop strange physical afflictions, like a second pupil in their iris, or bleeding from their eyes. And berserk homicidal tendencies, of course. Over the time, these minor affliction develop into serious bodily mutations- including tentacles, distended jaws, and reversible joints.
In Revenge of the Fallen, the resurrected Megatron has an enormous right arm—and a pitifully gimpy-looking left one. The enormous right arm is later torn off. In Dark of the Moon he's missing about half of his face, due to damage taken during the Final Battle of Revenge.
The elite Nazi mooks in Order of the Black Eagle have decidedly non-Nazi traits, such as flaming red hair worthy of a Celtic warrior of legend, or being as bloated as a sack of potatoes. The only elite mook who actually looks like a bonafide Nazi Aryan superman is, of course, the traitor. The amazing thing about this movie is that its made in the late 70's prior to any FPS game being released, otherwise the elites being markedly different would definitely have counted as a Shout-Out to FPSes like Wolfenstein, so it was simply a stylistic choice to remind you who the officers were.
Enter the Dragon has two examples: Mr. Han is missing one hand and likes to replace it with various killer prosthetics (such as a literal iron hand or the claws that inflicted the iconic scratch mark injuries on Bruce Lee's character). His Dragon, O'Hara, also has a jagged scar on his face that we soon discover was inflicted by Lee's father in an attempt to stop O'Hara from raping Lee's sister.
Star Trek II: The Wrath of Khan features Khan, the genetically augmented superman makes a spectacle of removing a glove from his left hand, but never removes the right glove throughout the rest of the movie.
Kinda in Inglourious Basterds with Aldo marking Nazi soldiers with a Swastika on their foreheads so that everyone will know what they did even when they are out of uniform.
In the early 90's Captain America film, Red Skull has a prosthetic hand, but had underwent plastic surgery to get rid of his skull-face.
In Surf Ninjas Colonel Chi has a mechanical arm, and this is used to make jokes obviously referencing Dr. Strangelove.
In the Star Wars films, people's eyes turn yellow when they become Sith. Emperor Palpatine also became further deformed when Mace Windu used the energy of his lightsaber to deflect his own force lightning attack back onto him.
Gremlins and its sequel feature this by way of showing some pre-Gremlin mogwai having extra tufts of hair: Stripe and Mohawk.
In The Dark Knight, the Joker has mouth-scars in the shape of a smile. In the 1989 film, his disfigurement was the result of getting shot through the cheeks before falling into a vat of chemicals, but then twisted further into a smile by a botched plastic surgery.
Frank D'Amico in Kick-Ass has an unusual scar on his forehead that looks like a cross between a spiral and parentheses. This is never explained.
In Mad Max, each member of the biker gang, including the Nightrider at the beginning, has a prominent facial mole.
In Dune, Baron Harkonnen has giant facial pustules. This was invented for the film, though both book and film versions of the Baron are morbidly obese. The Baron's weight in a prequel novel is attributed to a sexually-transmitted disease he contracted from the Reverend Mother after he raped her, and he later pretended to have gotten fat due to intentional over-indulgence so as not to appear to be a weak victim.
In Contagion, Krumweide (played by Jude Law) is given crooked teeth to foreshadow the revelation that he's a crook and a liar. His name also helps.
In Cube Zero, Jax has a cybernetic implant fitted where his right eye used to be. It's never shown or explained what abilities it gives him; it's only ever used to identify him as a villain and explain his hatred for machines via a Noodle Incident.
The Bug Alien in Men In Black disguises himself and attempts to pass as a normal human. But his disguise is the skin of a dead man that decays as the film continues. His appearance and behavior, as well as the presence of cockroaches all around him, make him quite villainous.
In A Christmas Story, local bully Scut Farkus has yellow eyes; his toady, Grover Dill, has green teeth.
Ralphie as Adult: There he stood, between us and the alley: Scut Farkus, staring out at us with his yellow eyes. He had yellow eyes! So help me, God! Yellow eyes!
One of the segments in the anthology horror film V/H/S follows a group of men picking up women in a bar. One of the women, who turns out to be a flesh-eating, batlike creature in disguise, is acting a bit off throughout the encounter but otherwise is quite normal except for a strange vertical crease in her forehead and scales and claws on her feet.
Played with in Thor- Loki's true Jotun form is blue, with red eyes and raised ridges scoring his skin. However, it doesn't actually disfigure him or make him look monstrous at all- he's basically a blue-skinned space prince, while the other Jotnar look monstrous, which probably was intentional, to help him maintain Tragic Villain status.
The Big Bad of Jack Reacher is a former Gulag prisoner who's blind in one eye and missing fingers on each hand.
Precision, from Hell's Children by Andrew Boland, literally has a red right hand. He also has a catastrophic plan.
President Snow from The Hunger Games wears flowers on his lapel to cover up the scent of blood. He suffers from mouth lesions caused by a botched attempt at poisoning his political rival. (Snow was compelled to quaff the poison himself, but managed to take an antidote before it killed him.)
In The Silmarillion, Morgoth has incurable burns on his hands from handling the Silmarils. He was also eventually stuck in a permanently frightening Evil Overlord form because he had become too weak and feeble to change his appearance to something resembling beauty.
One of the most literal is Red Grant of From Russia with Love, whose nickname besides referencing his allegiance to the Soviet Union, refers to his unpleasantly red skin tone which indicates the evil behind otherwise handsome features.
In Devil May Care the villain has gigantism in his right hand, making it resemble a gorilla's.
In Brokenclaw, the eponymous villain received his nickname because of a deformity in his left hand where his thumb is on the right (viewing the palm up) rather than the left, giving him two right hands.
The main villain of Derek Landy's novel Skulduggery Pleasant literally has a red right hand — that is to say, there is no skin on that hand, only muscle and bone. He can use this to channel a torturous killing curse.
The second and third books have Billy-Rae Sanguine, who has two black holes where his eyes should be. Creates a particular dissonance, since he is otherwise a fun-natured (albeit Ax-Crazy) Texan. Also the Faceless Ones cause the faces of those they possess to melt in a manner which destroys all of their features, the source of their name.
In Red Dragon and Silence of the Lambs, Hannibal Lecter had six fingers on his left hand (later in the series, he had the extra finger removed because it made him recognizable) and maroon eyes. Creepy.
The title character of Philip K. Dick novel The Three Stigmata Of Palmer Eldritch has horizontally slitted metal eyes, metal teeth and a mechanical right arm: all physical signs of his metaphysical transformation into something very other than human.
Hogfather, the villain Mr. Teatime is described as "quite pretty," except for his eyes: one is blank glass, while the other (considered far more disturbing) is yellow-white with a pinpoint pupil. (The page image is the film adaptation version of him.)
In other Discworld novels, transformed creatures cannot change their eyes. In Witches Abroad, Greebo retains cat's eyes in human form, and the Duc has to wear dark glasses because he's still got the eyes of a frog.
And the Cunning Man from I Shall Wear Midnight has no eyes - not blank skin or empty sockets, you just can see what's behind his head through the spots where his eyes should be.
With a snake-like face that nosedives into the deepest, darkest bowels of the Uncanny Valley, you can tell at first sight that Voldemort is evil.
Dumbledore's left hand is blackened and scarred after trying to remove one of Voldemort's curses. But Dumbledore is decidedly on the good side. It does represent his moral failings, though.
Peter Pettigrew, on the other hand sacrifices his hand to reconstitute Voldemort. He gets a beautiful silver hand in payment. But the hand is loyal to Voldemort only and ends up strangling Pettigrew to death when the latter hesitates—yes, only hesitates—out of a debt to Harry.
Similarly, Harry Dresden in The Dresden Files has one of his hands blackened and useless for several books. There was one area of his hand that wasn't burnt. And it was shaped like Lasciel's seal.
Jander Sunstar, vampire hero of Ravenloft novel Vampire of the Mists, got permanently scarred (in some sources up to the bone) hand after wielding the holy artifact of Lathander against another vampire, Strahd Von Zarovich.
In Chronicles of Thomas Covenant, Lord Foul's eyes look like "yellow, carious fangs", betraying his true nature. Significant in that his usual form is all but concealed but for those eyes, and when revealed but for them he looks pretty noble.
Outcast of Redwall features Swartt Sixclaw and his son Veil, who each have an extra digit on their left paw. Veil also ends up with a literal Red Right Hand, and red left hand too. He's tricked into staining them with beetroot juice in a trap set to find a poisoner which plays on his temporary Out, Damned Spot! mentality.
In Ursula K. Le Guin's Tehanu, a young and horrifically injured girl falls victim to this trope: a withered and nigh-useless hand, missing one eye, besides the fact she's traveling with a foreigner who brought magic items from a distant land while in the company of great wizards.
The titular character of the Vampire Hunter D series has a parasitic creature that takes the form of an obnoxious, ugly little face in the palm of his (left) hand. The symbolism is of a hero with inner demons.
In J. Michael Reaves' fantasy novel The Shattered World, the evil sorceress Ardatha has made a pact with a demon, which transformed her left hand into the likeness of a demon's hand, with claws and black scaly skin. The hand is the source of great magical power, supplementing Ardatha's own considerable power, and can glow with unholy fire. It's a source of both pride and terror for Ardatha.
Emperor Jagang is pretty thuggish looking anyway, but it is highly unusual and disturbing eyes which mark him out as something special and evil. They are totally gray, with no irises (though you can still tell when he is focusing on you apparently), with murky shapes moving across the gray.
Darken Rahl was also described as incredibly handsome except for his side, which was horribly burned. You can also tell by the way his name is Darken.
In the Deltora Quest series, the shapeshifting Ols must always travel in pairs, and have a mark on their body that they can't get rid of. And when you get to suspecting every pair of twins (and twin-like sorts) they come across... well, maybe you don't stop to think that the pairs don't have to look anything like each other.
A bogeyman-ish torturer in the The Seventh Tower series has half of his body replaced by a living mass of shadow. Of course, this is thanks to his boss removing that half of his body in the first place to ensure his loyalty, but that's hardly a burning issue to the people whose minds he's wrecking through their nightmares.
Sandor Clegane is first introduced as a thug, with half of his face grotesquely burned. This seems to be a Red Right Hand until further characterization shows how conflicted Sandor is, mostly because of his disfigurement.
Tyrion Lannister (loosely based on Richard III) in the minds of the people of Westeros. While Tyrion isn't a villain (yet), the fact that he's a particularly ugly dwarf causes just about everyone to view him as "the twisted little monkey demon" and the evil power behind the throne.
Victarion Greyjoy receives a burned arm up to the elbow as the result of some black magic healing. Afterwards, he becomes much more interested in human sacrifice and starts making some grand plans of conquest.
In the prequel novellae, Daeron II's bastard half-brother, Bloodraven, is a one-eyed albino, and widely blamed for the ills of the realm, up to and including murdering members of the royal family. He is a sorcerer, but his true motivations are currently unclear.
The Warlocks of Qarth all have pale blue lips and mouths from frequent drinkings of a mysterious liquid called "Shade of the Evening".
The psychopathic Euron Greyjoy wears an eyepatch to cover his "crow's eye." It's not clear what's wrong with his eye or what it looks like.
Averted with Crowley in Good Omens; he does have yellow snake eyes (hence the Cool Shades), but really is "evil" only by nature of his job description. Since he gets given human bodies to blend in on Earth, the implication is that he/Hell can't change these. He also has snake-skin boots that are implied to not be boots and he can "do interesting things with his tongue", both of which are suggestive of his origin as the Snake which tempted Eve.
The book version of The Phantom of the Opera has Erik's deformity cover the whole face, in that it makes his head look like a skull.
Inverted in the Warhammer 40,000 novel Grey Knights, where the Allking of Sophano Secundus and his retainers appear normal at first, but only reveal their Chaos mutations once the truth is guessed at.
In The Magicians, The Beast (AKA Martin Chatwin) appears completely human except for three or four extra fingers on each hand.
And the Big Bad in The Lost Symbol has tattoos over literally his whole body. When he goes incognito, any skin not covered by clothes has to be heavily coated in makeup to hide them.
The race of trolls in Goblin Moon and The Gnome's Engine appear mostly human, save that each sports a Red Right Hand or two (clawed hand, cloven hoof, fox muzzle, etc). These may be a legacy of their origins, as some claim they were once humans who became contaminated by their overuse of dark magic.
In a Pirates of the Caribbean prequel novel, there is a pirate named "Left-Foot Louie", who literally has two left feet.
Dimitri, the protagonist of a Brazilian novel released in English as Twelve Fingers: Biography of an Anarchist has... guess it. (and since he's really clumsy, they sometimes screw him over: he almost starts World War I, but jams both index fingers in the trigger, allowing for Gavrilo Princip to shoot... and the original title is The Man Who Killed Getúlio Vargas because the extra index "suicides" a Brazilian dictator)
In the Revelation Space novels, people infected with the Haussman Virus spontaneously bleed from their right hands in stigmatic imitation of the crucifixion of Sky Haussman, which helps in tracking a certain character through multiple memory gambits and deep covers
In The Lord of the Rings, about the only physical description given of Sauron's current form is that he is missing a finger on "the Black Hand." Said finger was the one that previously wore the One Ring, which was severed by Isildur in battle on Mount Doom. More immediately obvious is the fact that he was cursed with Shapeshifter Mode Lock after one of his bids for power, making him unable to ever again take a pleasant form.
The Witches, from the Roald Dahl book of the same name, all have completely bald heads, oddly shaped nostrils, long sinister fingernails, and - strangely - blue spit. For the most part, they manage to hide these deformities and blend in with society.
Brimstone Angels: Farideh's mismatched Eyes, one silver and one gold, and to a lesser extent her twin sister Havilar's two gold eyes and the horns, fangs and tails sported by both of them, are seen as this by many characters. They are tieflings (humanoids with a devil heritage) and as such are more than used to people thinking they are evil just because of what they look like. For many strangers Farideh's mismatched eyes seal the deal and put her firmly into Obviously Evil territory, despite the fact that she's not, and this has had a pretty noticeable impact on her personality.
The Vidiians on Star Trek: Voyager are victims of a flesh-eatng disease known as The Phage. They scour the universe looking for replacement body parts, reducing the whole lot of them to Mix and Match Men. This was later subverted in an episode where the Doctor fell in love with a female Vidiian, proving their species wasn't always malevolent.
Rankel, Ming's vizier in the 2007 remake of Flash Gordon, wears a long robe that obscures his legs, and does not walk, but rather glides along the floor. Additionally, and less subtly, he has a glass plate on his head which exposes his brain. In a twist from the usual, though, it seems he's going for a Heel-Face Turn, or has been plotting like The Starscream
Lucius Petrus Dextrus from the same series has a, er, petrus dextrusnote Latin for "stone right hand" of his own, but he's Genre Savvy enough to keep it hidden under a cloak. The Sybilline sisters are well on their way, too, but their symptoms are less extreme, more easily concealed - appropriate, as they're equally a little more neutral than Lucius.
Inverted in LOST, where Locke gets a Dr. No-like scar across his eye from the plane crash and was a paraplegic. He's the good guy until the last season.
Kenny on Kenny vs. Spenny is missing the tip of one of his fingers. Kenny often employs "evil" tactics like irradiating Spenny so he can't produce semen.
Thomas Barrow of Downton Abbey wears a glove to hide his mutilated hand.
In the Grand Finale it turns out the glove is hiding a literal red right hand.
Ankh from Kamen Rider OOO. To an extent. (As in, usually he is a literal red right hand, as that's the only part of his body that he's managed to restore. By attaching himself to the right arm of the dying Shingo Izumi, he is able to take over and have him as a host for most of the series.)
In Kamen Rider Kiva, Taiga, aka Saga wears one black glove. This hides the emblem on his hand that shows him to be King in the Checkmate Four.
In Buffy the Vampire Slayer, vengeance demons and Dark Willow are both explicitly described as "veiny". When Warren acquires a talisman of super-strength, Andrew is disappointed that it didn't make him "all huge and veiny".
In The Invaders (1967–68), the aliens (at first) can't bend their pinkies.
On Monk, the man who planted the bomb in Trudy's car has six fingers on one hand.
The song "Red Right Hand" by Nick Cave and the Bad Seeds is about such a character. This character goes around doing good deeds, giving people their hearts' desires, but only as the prelude to some unspecified plot. (The song was inspired by Milton's use of the phrase...which was, despite the vaguely Satanic implications of much of the uses of the trope and indeed the song itself, referencing God.)
You're one microscopic cog In his catastrophic plan Designed and directed By his red right hand
Lupe Fiasco's concept characters all have these. "The Cool" has a skeletal right hand, "The Streets" has glowing dollar signs for pupils, and "The Game" has dice for eyes and breathes out crack smoke.
The music video for Rammstein's song "Ich Will" has this - the band members perform a robbery, and most of them have a physical defect to show them to be the bad dudes - club foot, plastic hand, blind in one eye.
Laura Branigan's "Self Control" has a character with two red hands who tempts and seduces the singer.
The Lemon Demon song "Atomic Copper Claw" is supposedly about a person who's seemingly friendly, but is actually planning to murder the singer with the eponymous instrument. However, there's a fairly strong implication that the singer's just paranoid.
Used word for word in the opening stanza of "The Writhing South," by Say Anything. Not that the narrator's intentions are dubious in the first place, though.
The song "Worship You" by Vampire Weekend uses this phrase in the chorus. It is directed at a deity, most likely the Christian God, implying that he is not benevolent. This is a theme present throughout the album Modern Vampires of the City.
Mythology and Folklore
In old English myth, the barghest — a monstrous, ghostly black dog — could look like anything, but it would always have glowing red eyes.
In many old European folktales, the devil can take any form, but can't disguise his clubfoot/cloven hoof. Perhaps some sort of high heeled shoes?
The original ghouls of Arabic lore had a similar deal, only they couldn't hide their cloven hooves.
The somewhat less evil (though still dangerous) hulder of Norse legends looked like ordinary people, except that they had little cow tails. If they became "good," their tails would drop off (some versions also gave them a hollow back).
Similarly, Kitsune can't hide their tails, or in some variations, their tiny paws instead of feet. In some Chinese versions of the same concept, this inspired foot binding.
It was also claimed that Kitsune couldn't pronounce 'moshi-moshi' when speaking, even in human form. This led to the tradition of using 'Moshi-moshi' as a greeting in Japan.
In folklore of India the Rakshasa, tiger-headed demons, can masquerade as humans, but their hands always point the wrong way (palms up instead of down, and their thumbs point outwards).
In Eastern European folklore, the werewolf will have fur growing beneath his skin in his human form, fur that becomes visible when you cut him. Something Van Helsing got right, shockingly.
In Jewish folklore as well as some Eastern European traditions demons and vampires look like normal people except that they have bird's feet.
Several types of malevolent spirits in English and Celtic Mythology looked like horses or cows with hooves pointing backwards. Indian folktales had female spirits with the same defect.
Some scholars believe based on the last verse of Zechariah 11 that The Antichrist will have something wrong with his right eye and right hand.
Loki had scars on his mouth from a time when a dwarf sewed it shut.
In The Shahnameh, the tyrant Zahhak has a deadly serpent growing from each shoulder- an echo of his origins as a three-headed dragon in Zoroastrian mythology.
In the original vampire myths, vampires had a mutated left hand with scales and claws instead of skin and fingernails.
In the Dick Tracy strips, the most famous villains are the grotesque ones and their hideousness reflects the fact that almost all of them are unrepentant murderous scum.
Jillian Hall's original gimmick in WWE involved her having a huge "blemish" or "mole" on her cheek, which was apparently supposed to have been a reason for people to hate her. Unfortunately, it worked.
The Tzimisce do this to themselves using their unique ability of "Vicissitude", AKA "Fleshcrafting".
Also in Vampire, vampires from the Gangrel clan gained a physical animal trait each time they raged. A kind Storyteller would make you into this trope while a more vindictive one would have you sprout a tail or a frikkin' beak.
In the same universe's Demon The Fallen, the character Harvey Ciujilo (a.k.a. the demon Hasmed, a recurring character in the setting) has one normal eye and one eye full of blood and pus, referred to as his "Evil Eye".
Although the Soul Drinkers are good guys, many of them still have mutations from a close call with Chaos, providing a constant reminder of how close they came to damnation. Luckily, they have uses for them - Sarpedon stabs people with his eight spider-like legs, for example.
There is a deity called Kaela Mensha Khaine, the Bloody-Handed God. In 40K, the Avatar model is usually shown with a left hand that constantly drips blood. In the lore of the Eldar, the blood on his hand is from one of the greatest heroes of Eldar mythology whom he murdered, an act for which he was cursed.
Ubiquitous in the Ravenloft setting, where committing an evil deed and then blowing a Powers check wins you a Red Right Hand of your very own.
The demon lord Graz'zt is described as having shiny black skin, yellow eyes, fangs, six fingers on each hand, and six horns on his head. According to his entry on The Other Wiki, "These fiendish traits are apparent, regardless of whatever form Graz'zt chooses to take."
Members of the binder class in 3.5 gain power by channeling vestiges, and can end up with Red Right Hand traits if they botch the checks involved.
In Nobilis, Lord Entropy (a.k.a. The Darkest Lord, Imperator of Scorn, Desecration, and Destruction, and the leader of Earth's Imperators in the War for the survival of Creation) has hands that constantly drip blood due to the sheer evil of the deeds he has done in the service of Creation.
In Exalted, Infernals - who aren't necessarily evil but do tend to be somewhat inhuman and weird - typically have minor mutations from the demon that carried them their Exaltation and bonded with their flesh. For a pretty much literal version, there's the capstone Charm of Infernal Monster Style, One-Hand Fury, which turns one of your hands into a very nasty weapon...but usually causes it to transmute into stone or a monster's talon or something weirder, and even if you choose to leave it human in appearance, if it's shattered it gradually reforms into something blatantly inhuman. Abyssals have their own Red Right Hand in the form of their gradual adaptation into either a walking corpse or a terrifying alabaster beauty.
Older Than Steam: One of the paragons of this is William Shakespeare's Richard III, who has a whole set: hunchbacked, with an atrophied arm, one leg shorter than the other, and born with all his teeth already in place. After studying his recently discovered skeleton the real Richard III was discovered to have had scoliosis, enough to give him the nickname "Crookback" and make later generations think he was a hunchback, but the withered arm and mismatched legs is bollocks.
Almost literal in Friedrich Durenmatt's The Visit, in which Claire, the villain, has an artificial hand and foot to symbolize her inhumanity.
Averted with green-skinned misunderstood political activist Elphaba from Wicked. Of course, everyone thinks she's evil, even giving her the name Wicked Witch of the West, since it's a retelling of The Wizard of Oz. Played straight with her Yandere sister, wheelchair-bound Nessarose.
Parodied in Goethe's Faust, Part One: A witch is surprised that she cannot see Mephistopheles' cloven foot. Mephistopheles explains that he is using false calves. He does have a limp, though.
BIONICLE has Takanuva gain one when his light is drained, his right hand having shadow powers. The mix of light and shadow in him during that period creates a lot of conflict inside.
The Prince/The Tall Man of Chzo Mythos has no skin on either of his hands.
In Baldur's Gate II, the player must take a side in a mob war between a regular crime syndicate and a creepy lady with red eyes and a soft voice. Simply to drive the point home, she will only agree to meet you at the local graveyard, at midnight. Also, she has fangs. And not the nice kind.
In an expansion to Neverwinter Nights the player can opt for the Pale Master prestige class; one of the features of this class is that after a number of levels, the player's right arm is replaced with a skeletal arm which can kill foes with just a touch.
Inverted in Devil May Cry 4. Nero, the protagonist and all around good guy, has a red-and-blue-with-glow demonic right forearm that can project a spectral hand for several purposes called the Devil Bringer. He attempts to hide it from others at first by using a sling, but it eventually becomes public knowledge. It proves instrumental in defeating the demons that swarm Fortuna, and his love interest learns to look past the deformity and accept him for who he is.
Trias the angel from Planescape: Torment looks precisely as a being of pure good should... But his wings have burned away and been left a charred, skeletal frame.
Morphs in Fire Emblem 7 look completely human, except their pale skin and golden eyes give them away. One such character even earnestly believed herself to be human, but her appearance gave her away. Then there's Nergal's scar and exposed eye.
Sho Minamimoto has a black left hand and in his second incarnation, two black arms due to his being half Taboo Noise in The World Ends with You.
Rugal Bernstein, who gets a cybernetic hand and eye.
Wolfgang Krauser also bore an X-shaped scar on the top of his head.
Geese Howard has a sizable scar on his back that he shows off by removing his shirt before battle, gained when he was punted out a window at the end of Fatal Fury.
K' has a literal red right hand, as his real one was "incinerated" during the first "live firing" after Kyo's blood was infused into him. He's more of the Anti-Hero though.
Rugal again in his "God Rugal" form in the Capcom vs SNK series, has a real red hand.
Hitting the obscure, Doll Master from Threads of Fate had a massive, evil right hand of death.
In the Soul Calibur series, Nightmare has a bulky demonic right arm that is passed on to anyone he possesses. Siegfried's arm is restored by Soul Calibur, But it looks like Pyrrha's is only going to fade away given time to heal after she turns good again.
In the Geneforge series, canister addicts have faintly glowing skin and cold, glowing eyes. Those that have been using canisters for a long time have translucent skin, with their glowing muscles visibly reshaping themselves at all times.
In inFAMOUS, Kessler has a mechanical gauntlet covering his entire right arm, presumably to enable the long-range energy blast he uses in his boss fight. His Psycho Ex-Girlfriend Sasha basically has Cthulhu for a tongue.
I don't know if this was the same in the old version, but in Tomb Raider Anniversary, the first time you see Natla, you know she'll be the villain. The really really long nails are a dead giveaway. Did I mention they were bright red, too?
Not to mention that rather long (yet surprisingly sexy) face with the sharply slanting eyebrows.
The Legend of Zelda: Even as a normal human Ganondorf had unusual green skin. How green depends on the artist and game. Chancellor Cole in The Legend of Zelda: Spirit Tracks has twin top hats worn on his head, which very obviously cover up the devil horns he's seen with later. And reverse colored eyes.
You don't really need any sort of hint concerning the Overlords of the Overlord series, what with their spikey, face-concealing helmets, the Shoulders of Doom, clawed gauntlets, etc. all quite obviously screaming "villain" from the CD cover. But considering the title, do you even need the hint?
The Overlord of Overlord II has blue skin as well, but this is the result of the old tower heart blowing up around the time he was born.
Yuri in Command & Conquer: Yuri's Revenge. Bald guy with tattoo on the forehead? Check. Cybernetic implant? Check. Evil goatee and mustache? Check and check. Psycho gaze? Check. Creepy voice? Check. Performed by Udo Kier? Check.
Team Fortress 2: the Engineer has a mechanical right hand. According to canon, he severed his own flesh and blood hand in order to replace it with a machine one that his grandfather designed. Somewhat averted, though, as Engie is still more or less the nicest guy on the Team. (Which isn't saying much.)
In the Kingdom Hearts series, anyone completely immersed in darkness, including all incarnations of Xehanort, have striking amber eyes. Tellingly, the amnesiac Xehanort inhabiting Terra's body doesn't have them. Oddly, the real Ansem the Wise has them too, which makes his true identity somewhat of a mystery throughout Chain of Memories and Kingdom Hearts II.
The Dragon from Deus Ex, Walton Simons, has unpleasant-looking blue veins covering his skin as a result of his nanoaugmentation upgrades. (It's implied that JC and Paul would, too, if they shaved the sides of their head like Simons does—they certainly have similar markings elsewhere.)
In addition to the deformities of villains present in the comics and other media (Two-Face's scarring, Joker's bleached skin and green hair, Poison Ivy's green skin etc), the Penguin's monocle is replaced by the base of a bottle that was jammed into his eye by an angry customer at the Iceberg Lounge before the events of the game, and stayed there.
The Joker also gets his awful rash from the toxin.
Played straight in Golden Sun: Dark Dawn. Blood Knight Blados has strangely-colored skin and red eyes (initially fueling theories that he was from Prox, which were incorrect), and his partner Chalis has demonic horns. Even with Golden Sun's track record for subverting villain tropes, these two go way too far for any amount of redemption to save them.
Ghetsis's telltale red monocle is revealed by concept art to be covering some pretty nasty-looking scars. His right arm is kept hidden except in the intro, where it's strangely discolored.
Handsome Jack in Borderlands 2 has surgical clamps and visible seams running along the edge of his "face", along with heterochromia. After killing him, players can actually loot his mask and wear it. Depending on the characters it looks either really awkward or really creepy.
In Crysis 3, the Nanosuit's replication of Prophet's human body would be perfect if not for the glowing bits in his eyes.
In Puyo Puyo, one of the main characters, Sig, has a red left hand, complete with heterochromia. Inverted in the sense that he is peaceful, absent-minded, and cares about nothing except insects.Implied to be played straight or slightly averted if you think a LOT about Strange Klug's backstory.
Fate/stay night: True Assassin aka Hasan-i-Sabbah sports a literal example of this. Its primary use was to assassinate targets by making a fake heart of the target out from ether and then crush it, destroying the original along with it.
Justice for All: The Big Bad is your defendant, Matt Engarde. He looks innocuous enough, until he pulls The Reveal, which consists of giving himself a phone call, pulling back his hair to reveal scars on his eye, and pulling a glass of brandy out of nowhere just to swirl it around while grinning evilly.
In the final case of Apollo Justice: Ace Attorney, Kristoph Gavin has a scar on the back of his hand that looks like a skull when he flexes his fingers a certain way.
While not an unusual feature, Dahlia Hawthorne's red hair is the only difference between her and her good-natured twin sister Iris.
Shelly De Killer has stitches down the middle of his face.
Phoenix: A baseball has stitches! Are you saying all baseballs are suspicious because they have stitches?!
In Charby the Vampirate, the author has a right red hand (complete with black spikes and claws!) added to her sexy and nice self portrait in the first page to remind everyone she draws a wickedly evil webcomic that kills characters off AFTER they've been around long enough for you to get attached.
In Webcomic/Comedity, one of Garth's personae, number 47, literally goes by "The Red Right Hand" and while not strictly evil is all of Garth's violent tendencies embodied. Hello again, Natalia.
In Cura Te Ipsum, main antagonist Dark Everett, "cut off his own nose to spite his face."
Dominic Deegan: Dominic's older brother Jacob is missing most of the flesh from one arm and the bottom half of his face due to his screwing around with necromancy. Though it's been restored a couple times, as well as being turned pitch black (momentarily) by absorbing pure undiluted Undead Blight.
Eventually Jacob gets his body completely restored, and seems to be keeping it that way after a Heel-Face Turn.
Nature of Nature's Art: SV spends quite a bit of time in self-imposed exile, seeking the power of malice... and that ended up taking priority over his own well-being. So when he returns to civilisation, his fur is really messy, his incisors have become extremely long (and they curve out of his mouth in an unnatural way), and one of his eyes... well, it's either completely red or completely black. The greyscale art makes it hard to tell.
Trace of TwoKinds has ended up with a black and clawed left hand (sinister, huh?) after using potentially mind destroying dark magic.
Drucilla the shape-shifting succubus of Pibgorn (from the creator of 9 Chickweed Lane) has reddish notched elf ears that she can't alter even if she's just in other people's dreams.
In Homestuck, whoever wears one of the Queens' rings gain physical features of each player's prototyped spirit; ie, wings, long tentacles and a sword through their torso. After Jack becomes the only one left wearing the ring, he gets a literal Red Right Hand. It's covered in the blood of WV, who Jack punched through the stomach to get the uranium he ate.
Many characters, including Jack, are also missing an arm and an eye. Not all of the others are evil, though.
Averted with Clinton from Questionable Content; he has a very obvious prosthetic hand, but he's not evil, just overzealous and a little unintentionally creepy.
In Genocide Man, Genocide Men (and women) have all-white eyes.
Linkara's robot double Mechakara in Atop the Fourth Wall has a mechanical left hand. Which makes for an absolutely wonderful piece of foreshadowing later on.
The Fear Mythos gives us "Jack of All," a man with a literal Red Right Hand. Interestingly, his appearance changes depending on who he's trying to strike a deal with, but his red hand remains a constant (though sometimes, he only wears a red glove over it, whereas other times it may be simply a red-colored human hand, and occasionally, he has a misshapen red claw)
Parodied by the Onion with Dr. Lester Mordock and his army of super-crabs.
Commentator: You know, it's so inspiring the way he found success after that tragic military accident that left him using a robotic claw for a hand.
In an episode of The Simpsons, a cigarette company executive has horns which he tries to pass off as a football injury. He also occasionally turns into a gigantic red devil.
Mozenrath, a villain in Disney's Aladdin: The Series, wears a magic gauntlet that stripped away the skin and muscles of his hand leaving a skeletal hand that still continues to feel pain from the gauntlet. He's furious that Aladdin got "easy" power through his Genie, as opposed to the sacrifice he made and suffering he endures.
Most of the villains and villainesses in Jacob Two-Two have poor dental hygiene and off-white eyes. Those that don't are unbearably clean smug snakes.
A one-shot Dungeons & Dragons villain, Queen Syrith, in the episode "Child of the Stargazer", had a literal red hand (it eventually turned out that an entire half of her body was like that, but her hand was her only visible deformity for most of the episode).
In Avatar: The Last Airbender , Zuko's scar and hair are used to mark him as a bad guy. After turning good, he changes his hair to make his scar look less ugly. We also find out that he got the scar from his father as punishment for what was actually a Pet the Dog moment; the scar is actually proof that he is redeemable.
Bato, one of the Southern Water Tribesmen has a large red burn on his right arm and hand. (Probably from an encounter with a Firebender.) He however, is a good guy.
Both Combustion Man's right forearm and lower leg are prosthetic. It's implied this is because he blew them off while learning to master his special firebending talent.
Blackwolf, the scenery-chewing villain of Ralph Bakshi's 1970s sword-n-sorcery opus Wizards, takes this to such an extreme that he is almost The Grotesque. His skin is grey, his eyes are blood red and glow in the dark, and — inexplicably — both his arms are bare bones between wrist and mid-bicep.
In its spinoff, She-Ra: Princess of Power, one of the main villains was a sorceress named Shadow Weaver. She was actually a student (and, it seems, a rather pretty one) who was tempted by the Horde to receive the power of an ancient crystal. It was destroyed after she absorbed one third of the power, which turned out to be enough for... well, she shows one potential student a glimpse of her face, and it's a Take Our Word for It scene.
Doctor Blight, one of the major Captian Planet villains was perfectly normal, even icily attractive...until she moved her fringe, and we saw that all the face around her left eye was hideously burned. All the other villains took this so far as to become grotesques (Verminous Skumm was literally a rat-man) except for Zarm, who was a standard Evil Overlord, and Looten Plunder, who was a Smug Snake crossed with a Corrupt Corporate Executive, though the fact that his suit was trimmed with what appeared to be zebra skin might count as an eco-sensitive version of this trope.
Phantom Limb has both arms turned into invisible glowy dispensers of death. His legs, too. And "something else" that The Alchemist decided to keep at the end of season 2.
Baron Ünderbheit has a prosthetic iron jaw and hideous grey skin.
Minor villain Scaramantula has a scar or birthmark shaped like a spider on his face and eight fingers on one hand. Brainulo (a hyper-intelligent time traveller from the future) has a grotesquely swollen, bald head covered in little blinking lights. Even the Monarch, while otherwise normal-looking and even handsome, has long antenna-like eyebrows.
While not visual, Dark Mistress Doctor Girlfriend has a man's voice. It's a smoker's voice, technically.
Spoofed in the episode "Now Museum, Now You Don't", where, in a flashback, Scaramantula assembles a Fraternity of Torment of villains who were spurned by society due to their deformity. Dr. Venture Sr. infiltrates them disguised as a stereotypical Chinese/Japanese villain with a supernumerary nipple (on his chin).
Akin to the Venture Bros. "Fraternity of Torment" example is Chairface Chippendale, foe of The Tick, and his speech to his cohorts about their various deformities uniting them in evil.
Shego has a greenish cast to her skin and hair and can shoot green plasma from her hands. (Originally this was written as being due to gloves, but they turned out to be her own powers.)
Drakken has pale blue skin as well, but he can't shoot anything out of his hands. Apparantly he's blue simply because he is evil, as in one episode him and Ron switch moralities through a machine (don't ask) and Ron turns blue while Drakken looks like a normal person for once.
Monkey Fist's surgically attached monkey hands and feet.
Sheldon "Gemini" Director has a prosthetic hand that launches miniature missiles.
Van Kleiss, Big Bad of Generator Rex, has a mechanical left hand that's made far creepier by the fact that its nails elongate into the syringes he uses to leech the nanites he needs to survive out of his victims.
The Argentinian cartoon Las aventuras de Hijitus by Manuel García Ferré had a villain called "Dedo Negro" (Black Finger), a master of disguise easily who despite his uncanny ability to pass as other people, was identifiable by his black left index finger. One of his exploits included, with the help of Professor Neurus, to hammer all people's index fingers in the city of Trulalá (!) to render impossible the identification by this means. More information here.
The age old stereotype against left-handed people. Sinister comes from the Latin word for "left", and "dextrous" from the word for "right" in all senses. Possibly related to two things: first, the old-fashioned rule-of-thumb hygiene standards that are still used in modern strict Islamic regions: left hands are for wiping, and second, the handshake. While today we clasp and shake hands, the tradition in older civilisations was to grasp the forearm of the person you were greeting and vice-versa, which demonstrated that there really was Nothing Up My Sleeve to both parties. Unless, of course, one of those parties was left-handed, in which case they could be concealing a weapon there.
Asian superstitions say that the aswang, a vampire-like demon, can be recognized in human form by the lack of the crease between nose and mouth, and an inverted reflection in their eyes.
The French word vilain, as an adjective, means "ugly". As a noun, it can mean, loosely, "bad boy". It descends from the same Medieval Latin root as the English word Villain - villanus, which means... Farmhandnote (alternatively, scoundrel or knave).