"Likewise, in fiction, whatever power a character has must have a downside somewhere, or he becomes a boring Superman type of character who can handle anything and get out of any difficulty, and he won't interest readers for long."
In Fairy Tail, Natsu is a very powerful mage who often defeats his opponents handily. He, however, is completely incapacitated by motion sickness when on any mode of transportation (including piggy backs). This was even actively weaponized against him at times, such as when a villain lured him into a shallow river and rigged a raft from underneath his feet, instantly bringing him to his knees.
This weakness of his is at least partially a psychological one, as he only falls ill on anything that he believes to be transport. Thus, since he doesn't consider Happy the cat to be transport, he can fly with him.
It turns out that all Dragonslayers eventually develop this weakness.
Wendy has this in the form of sour foods, like dried plums. She was once defeated simply by watching someone eating dried plums.
In InuYasha, the titular character temporarily loses all of his demon-powers on nights with a new moon.
There's also Miroku, who has a miniature black hole that is initially a game breaker. So the show introduces poisonous wasps which can kill him if he sucks them up. These practically become the villain's trademark so that only Inuyasha can be a credible threat to him.
In One Piece, anyone who has eaten a Devil Fruit has two, related Kryponite Factors: The ocean, which causes power leeching and an inability to move due to weakness, and Seastone, also known as Kairouseki or as "Sea Prism Stone", which replicates the effects of the ocean and out of which most prisons in the One Piece world are built.
The effect of Seastone and the sea itself varies from user to user: Luffy (a paramecia user) and Chopper (a zoan user) have severe and painful reactions to either but are still made of rubber (which is used to save his life when he's drowning in the ocean) and a human-zoan respectively while logia fruit users and other paramecia users are simply unable to use their powers
Smoker also has some Kairouseki on the end of his jotte, despite his being a fruit user himself (the weapon is long enough to keep him from coming into direct contact with the stone).
The Yami Yami no Mi also appears to act as kyrptonite to devil fruit users and seems to have been built just to combat them: of the 3 abilities shown so far; creating black holes (and expelling anything pulled in), pulling in devil fruit users and canceling fruit powers only the first can be used on normal people.
Busoushoku no Haki (Armament Haki) allows the person who use it to surround himself/herself with a thin air but powerful armor (it's mostly invisible until the Time Skip), allowing the user to negate devil fruit powers by contact. It does not cancel the devil fruit power itself, but it's one of the few only methods to attack and hurt logia-types. Trained Haki users can use their Busoushoku Haki for their projectile weapons or devil fruit powers.
In Dragon Ball, the main protagonist Goku severely weakens when he does not eat for long periods of time. Also, his original race, the Saiyans, usually posses a common weakness; if their tail is pulled, they will be rendered completely immobile. However, the Saiyans ability to adapt in battle allows them to adapt this weakness away so it is not that significant.
In fact, in Dragon Ball Z, this weakness is only ever successfully exploited in a single episode. It is only ever tried one other time, and never used or mentioned again.
In Dragon Ball, Goku eventually toughened up his tail by constant training (before eventually losing the tail permanently). One presumes that Vegeta and Nappa had done the same.
Anpanman has a head made of bread, which is his weak point. If he breaks of too many pieces of it to feed others, or his head gets wet, dirty, bruised up, or moldy, he loses his power. Once a new head is put on, he gains all the energy he needs again.
In A Certain Magical Index, Saints are people born with physically perfect bodies similar to the Son of God. This gives them great powers like incredible levels of Super Strength, Super Speed, Super Toughness, etc. However, they are vulnerable to any of the tools that were used to torture Jesus. For example, if an ordinary person punched them or hit them with a baseball bat, they could easily shrug it off. But if a Saint was hit with a cross, crown of thorns, scourging whip, etc, the item would hurt them like it would a normal person. There are also spells designed to combat Saints, like the appropriately named "Saint Destroyer".
In Black Bullet, the monsters known as Gastrea are practically invulnerable to normal weapons, but weapons and bullets made of the metal Varanium can harm them, and monoliths made of Varanium can drive them away. However, there are Gastrea that are powerful enough to ignore the monoliths.
Superman is the Trope Namer of course, with his weakness to Kryptonite (radioactive Green Rocks from his home planet) established back in the 40's. Since then, he's gained a few other vulnerabilities: he has only basic resistance to magic (though some authors treat magic as a bona fide weakness for him and his kin), red sun radiation can temporarily rob him of his powers, and there's a whole spectrum of coloured Kryptonite with varying effects (from Red Kryptonite that causes a random change for 48 hours, to Gold Kryptonite that robs him of his powers permanently). He can be killed by a huge amount of brute force, as seen during The Death Of Superman, though of course he turns out to be Only Mostly Dead.
Of course, Doomsday was also from Krypton, leaving the reader to wonder if that gave him some sort of edge over the Man of Steelnote the canonical answer is "no". It was mostly due to the fact that the fight dragged out into the middle of the night; without a source of solar radiation to replenish his powers and heal injuries, Superman just ran out of juice.
The Gold Kryptonite part is now "powerless for 30 seconds", mostly so it wouldn't be overused.
He even has at least three villains — Metallo, Conduit, and the Kryptonite Man — possessing powers that boil down to being Kryptonite. And now that Gold K has been Nerfed, minor villain Radion has been revised into this as well.
Superman also had problems with Red Kryptonite, special kryptonite that could randomly alter Superman's powers, doing anything from making his hair grow to actually slowly killing him.
In fact, Brainiac once used a special mix of red and green Kryptonite that gave him a third eye in the back of his head. In order to protect his secret identity, Supes pretended that the kryptonite had addled his brain to make him wear whatever hat is near him.
One Superboy story had him meet Mon-El, an amnesiac with powers like his, who assumed due to this that he was Kryptonian. Near the end of the story, Clark gets suspicious and lobs lead boulders painted to look like Kryptonite at him. Mon-El collapses, and Superboy flies in to accuse him of fakery — but the trauma has brought his memory back; he's a Daxamite, a member of a race similar to Kryptonians, but with a weakness to lead poisoning instead of Kryptonite. To keep him from dying, Superboy puts him in the Phantom Zone, preserving him for a thousand years until the Legion of Super-Heroes finds a cure.
Later retellings have Clark and Mon-El seeing if Mon-El was a Kryptonian (whose memories were slowly coming back) and Mon-El getting sick after Clark takes out a lead box containing some Kryptonite, mostly so it doesn't make Superboy look like a massive dick.
The color yellow was/is a major weakness to the Green Lantern Corps. This was eventually explained by the influence of a fear demon the creators of the rings had entrapped corrupting their powers, but also authorically served to constantly remind them their potential godlike power has limits (a Green Lantern Ring being otherwise limited only by the intelligence, creativity, and willpower of the wielder). When Kyle Rayner was the only Green Lantern, thanks to Hal Jordan's Brainwashed and CrazyFace-Heel Turn, his ring had no vulnerability to yellow. However, when Hal was brought Back from the Dead and the four Earth Lanterns took down Paralax, the Entity of Fear (and thus, the Yellow Impurity that prevented Lanterns from harming yellow objects), it was reinstated and Ret Conned that Lanterns can overcome the weakness by recognizing fear.
Alan Scott, the Golden Age Green Lantern, had no vulnerability to yellow, but a similar vulnerability to wood. This was due to his more magical ring being connected to "green, growing things".
This was retconned into a long story involving one of Earth's first GLs. He was mad with power, so the Guardians gave him the wood weakness so primitive humans could club him to death. However, instead of dying, he put his soul into the power ring and battery, which collided with a Meteorite, becoming the Starheart. Alan Scott got his ring from the Starheart. Seriously.
The entire 'wood weakness' may have been a Retcon itself; some of the earliest comics indicate he has 'invulnerability to metal' but not really anything else, allowing him to be, among other things, knocked unconscious by a teak vase.
It's worth noting however that because of this on-again/off-again vulnerability, the fact that Sinestro always has a yellow power ring is almost a Grandfather Clause.
Not quite. He was assumed to be dead while the fear entity was out doing whatever fear entities do.
In the Elseworlds storyline Superman & Batman: Generations, it was revealed that the yellow vulnerability was just a hoax made up by the Guardians to keep the Green Lanterns from getting too cocky. Alan Scott's wood weakness, however, was psychosomatic and imposed by himself; during his early adventures, while fighting some ruffians, one snuck up behind him and hit him with a wooden club. While the truth was that he just didn't pay attention and thus allowed the foe to get in a cheap shot, he instead convinced himself that he had a weakness to the wood and thus couldn't defend himself. Guess he had a bit of an ego going...
The Blue Lanterns are a bit different. Instead of having a weakness to another color, the Blue Lanterns are dependent on another color, namely green, in order to use their powers effectively. This is because green is the color of willpower and blue is the color of hope. You can hope all day long that something good will happen, but that won't accomplish anything unless you also have the will to help your hopes come true.
The Martian Manhunter (who is both powerful and has a variety of useful powers) has a vulnerability to fire. And a rather powerful addiction to cream-filled cookies, though this is more a comedic device. (See 2000's Martian Manhunter #24). In The Silver Age of Comic Books, fire was treated by him as equivalent to Superman versus kryptonite, but Post-Crisis, it became more of a crippling phobia. (They seem to keep going back and forth on this one.)
At least once, his fire vulnerability was explained by saying that he almost died in a fire once, and has feared it ever since. This falls apart when one considered that every Martian who's ever appeared in DC Comics has been vulnerable to fire. Current canon is that it's a genetic block implanted by the Guardians to lock away the burning Martians.
Early versions of Wonder Woman had her lose her powers if she was tied up by a man, under "Aphrodite's Law", leading to some bondage imagery that must have been blatant even at the time of its introduction. As noted in her entry, that was quite deliberate. In The Silver Age of Comic Books, she went into an Unstoppable Rage if her bracelets were removed. Currently, Wonder Woman has no Kryptonite Factor weaknesses.
Partly because she is not as invulnerable as Superman or Manhunter. Bullets can penetrate her skin if she doesn't block them with her bracers and she needs to breathe, just as examples.
She does (or at least did - her continuity is a moving target) lose her powers when she changes back to her secret identity, thanks to a spell cast by her Arch-Nemesis Circe. Which raises the question of why she ever turns back to her secret identity, given that they look exactly the same. The only possible benefit to transforming is that it saves her the trouble of changing clothes.
In one story (as in, within the past 10 years - not exactly yesterday, but well after Crisis on Infinite Earths) story, Batman defeated an Amazon footsoldier by throwing a magnetic baterang at her, which stuck her bracelets together when she blocked it and removed her powers. Suggesting both that the weakness is common to all Amazons, and that it survived into the modern age ... or possibly that whoever wrote that story was taking a few liberties.
This was actually used in one of the incarnations of Superfriends - Scarecrow had captured Wonder Woman and Robin in an attempt to lure Batman into a trap. When Bats arrived, Wonder Woman had her bracelets fused together, thus rendered powerless.
In Preacher, Jesse Custer's power of the Word (his ability to force people to do what he says) has a catch: the Word must be both heard and understood to work. Among other things, this means it doesn't work on animals, various characters avoid it by covering their ears, and at one point it's rendered moot when a squad of soldiers who only speak French are sent after him.
In X-Men, Cyclops' optic blasts can be entirely contained by even a thin sheet of ruby-quartz (and, uh, his eyelids apparently) This is used to his advantage, as he can't normally control his optic blasts at all, and so wears glasses with lenses made of the material. Occasionally a villain will strap some ruby-quartz armor, or lock a quartz helmet on to Cyclops's head, but usually they prefer to go the route of knocking off the glasses.
His brother Alex is also immune to his powers, as is he to Alex's. This is explicitly a result of the shared Required Secondary Powers that stop them from blowing themselves up.
Wolverine, X-23 and some other fast healers in Marvel, have trouble healing when having "strange (or foreign) metals (or substances)" on their composition (such as Wolverine's adamantium skeleton, or being struck by carbonium) and thus not heal as fast (read: instantly)
The New Gods of the DCU, while far from completely invincible (with the exceptions of the stronger ones like Darkseid) are all vulnerable to the very rare element Radion. In Final Crisis Darkseid kills his son Orion with a time traveling Radion bullet. Batman later fires the same bullet into Darkseid to fatally poison him; an act that eventually leads to Darkseid's Final Death.
Common vulnerability of aquatic superheroes like Aquaman and the Sub-Mariner is the need to remain hydrated (moreso than a normal person, that is). Generally, it's relatively mild - the need to be submerged in water at least once every 24 hours, for example - and comes up more as a way for villains to keep them prisoner than as something they need to worry about on a regular basis, but it does make them extra vulnerable to villains with heat-based powers, and a Crazy-Prepared villain will always find a way to exploit it (Aquaman was once made to be afraid of water, for instance).
Aquaman's hydrophobia is especially notable because it was brought about by Batman. That was one of the stories that solidified his status as Crazy-Prepared.
There is a certain gas that can remove Spider-Man's Spider-Sense temporarily. It is often used by the goblin-based villains (Green Goblin, Hobgoblin etc.) or by Mysterio. Venom and Carnage are completely immune to the sense altogether, since their powers come from the alien suit Spider-Man wore. Removing his spider sense or being immune to it is always shown to be disastrous for Spider-Man. For instance, his Aunt May is immune to his spider-sense due to being a trusted family member. Trying to get to his bedroom, he snuck into her house one night, still dressed as Spider-Man. She managed to sneak up on him and ended up whacking him over the head with a vase, KOing him.
One of the plot points in Spider-Island was Peter temporarily losing his Spider-Sense and realizing just how much he depended on it. He spent some time training with Iron Fist to become less reliant on it.
Inverted with The New 52 version of Ultraman. He gets stronger by consuming kryptonite. However, sunlight weakens him. To counter this, he creates a solar eclipse after being amped up on kryptonite.
The title character of Bolt is a dog on a TV show who thinks his superpowers are real. When he is accidentally placed in a box and shipped to New York, he finds that he no longer has superpowers, and thinks the Styrofoam peanuts in the box are the cause of it.
Lampshaded in Unbreakable. David is a horrible swimmer and nearly drowned once as a kid. Discovering this was evidence reinforcing that he was actually "unbreakable" because all heroes have some sort of weakness. Another character points it out to him, saying "that's your Kryptonite."
In a dream sequence in Harold And Kumar Go To White Castle (aka H&K Get the Munchies), the bullying sheriff gets to say this terrific line after he gets shot: "Bullets! My only weakness! How did you know?"
In Who Framed Roger Rabbit, Toons are invulnerable to conventional damage, but can be injured or killed by a specific blend of paint-and-ink-thinning chemicals, known as "the Dip". Immersion is fatal, and a Toon cab who'd skidded through a puddle of Dip suffered four flat tires and was left limping in pain.
They also can't let the ol' "Shave and a Haircut - Two Bits" go unfinished. Roger ends up ruining their hiding spot because of it.
Lampshaded in Sky High - instead of arbitrary medical checkups, students are exposed to Green Rocks of different colors to check for weaknesses.
All superheroes in Up, Up, and Away are weakened by tin foil. Too much is fatal. When the main character's friend brings over a meal that's wrapped in foil, the parents (all supers) treat it as a bomb and then bury it in the yard. Of course, the Big Bad finds out about this and then goes to the nearest grocery store.
In Mega Mind, the eponymous villain accidentally defeats Metroman by trapping him in a room lined with copper, his previously unknown weakness. It turns out to be a trick to allow Metroman to fake his own death.
Exposure to Krypton's native environmental conditions weaken and at first even incapacitate Superman.
Zod's Kryptonians similarly initially lose control of their powers and pass out while trying to adapt to Earth's native atmosphere.
In Lemonade Joe, Joe is a strong, tough guy with Improbable Aiming Skills. There is one substance that is his Achilles Heel and makes him lose consciousness, leaving him at his enemies' mercy. It's alcohol.
The Alteriens of Adam R. Brown's Alterien are pretty powerful, but they too have their weaknesses. Iron objects can hurt Alteriens, going so far as cancelling out their ability to absorb kinetic energy. As such, an Alterien can be cut or even killed with iron. It is of note, however, that it takes far more than a cut to kill an Alterien. It would take the same amount of effort as it would for a human using an ordinary knife or sword. This means an Alterien can die if beheaded or cut in half by an iron blade or stabbed multiple times with iron to the point of overtaxing their healing factor. Alteriens such as Oberon are also vulnerable to areas of concentrated dark psychic energy. Whenever Oberon is in or near such an area, he becomes very weak and his ability to absorb energy is reduced.
Star Wars got in on the act in the Expanded Universe by having creatures who "pushed back" the Force (in the case of the ysalamiri), hunted with the Force (thereby making them far more aggressive around Force-users, as with the vornskrs), or who had been "severed" from the Force, and so were unable to be sensed or affected by the Force (like the Yuuzhan Vong). The idea, of course, was creating handicaps so that a simple kidnapping plot, for example, would work against Jedi, who would normally be able to shrug off drugs, sense someone walking up behind them, open locked doors, etc.
Let's not forget the mighty lightsaber's weakness: the totally useless space-metal cortosis, which renders a lightsaber useless for a few seconds.
Oh and for most you can't immerse them in liquids without the blade switching off. Rain's fine though, and Jedi from water worlds fix this problem with some modifications.
Lightsabers have another weakness as well. Bullet based weapons (called "slug throwers" in universe) can't be reflected by a lightsaber as blaster bolts can. All it does is melt the projectile, which means instead of a Jedi having a speeding bullet coming at their face, they have a piece of liquid metal coming at their face.
Parodied by Captain Underpants, who thinks he loses his powers when he's sprayed with starch. It's actually a Placebo Effect, because he only believes it because that's what George and Harold wrote in their comic book.
Crucial in Steelheart, where every super-powered "Epic" has a weakness that will either cancel out their powers or at the very least make them vulnerable to physical attack. Sometimes it's as straightforward as being close to a particular kind of metal, but others get crazier - like one who the characters mention could only be killed by people who are 37 years old.
Because the writers of Smallville have small[ville] imaginations, they are unable to construe ways of having Clark Kent face danger without invariably introducing some form of the Kryptonite Factor. They did bring up Clark's vulnerability to magic but rarely use it because of how much one can stomach magic in a thematically sci fi show. This led to the Green Rocks factor exploding with Kryptonite being used for nearly every villain's plot so that it had some reason to be around, e.g. Kryptonite being needed to print money.
Although this formed a mutually Justified Trope with the Smallville Monster of the Week format. Kryptonite produced the baddie/misguided teen that Clark went up against each week and they were actually a challenge (it's hard to use your telepathy to cheat on midterms if Superboy had already punted your ass into the next county) because they were fueled by Kryptonite.
Parodied on the Nickelodeon sketch comedy show All That, where recurring character Superdude's weakness was "lactose intolerance", meaning in his case that merely being in the proximity of dairy products was harmful to him. Naturally all of his opponents were dairy themed.
Or would fight in an area where dairy products would be common. Such as a cow barn.
Another All-That villain got his powers from radiative materials stored in a bucket that landed on his head. Problem was, he couldn't get the bucket off, and his blind attempts at heroism were often... less than ideal.
Non-super example: James May of Top Gear appears to have mild to moderate obsessive-compulsive disorder. His co-presenter Jeremy Clarkson once drove him offstage by rotating the bezel on his watch until it was out of alignment with the face
In Doctor Who, the Doctor's sonic screwdriver was notorious for having no specific guidelines or limits to how it could be used, so much that lazier writers would rely on it too much as a Deus ex Machina to get the Doctor out of any predicament. The Fifth Doctor broke it and went hands free. When the series returned in 2005, two very specific limitations were put on it: a), the screwdriver can't break through a Deadlock Seal, and b), "it doesn't do wood". The latter has been repeatedly lampshaded as "rubbish".
For Sportacus from LazyTown, it's sugar; eating any sugary food renders him immediately comatose, and fresh fruit (despite having a high sugar content) or vegetables (a classification that includes the Sugar Beet) are required to restore him.
Cole on Tracker was vulnerable to Lodestone - it interfered with his life force sensing ability and weakened him a bit.
In Supernatural, salt can stop most monsters. Demons can not cross a line of salt. Ghosts are repelled by salt. Fairies have to count every grain of salt if it is spilled in front of them.
In Arrow, people who've taken Mirikuru are almost unstoppable; bullets and arrows do nothing and they're strong enough to overpower anything. Their only apparent weakness seems to be explosives; even small ones tend to knock them out for a bit to deal with them. Somewhat downplayed, however, since explosions are likely to kill anyone, but its notably the only thing that's been able to deal with them more than once.
Mythology, Folklore, and Religion
The Chinese tale of the Ten Brothers has ten brothers all born with supernatural powers that they lose when they come into contact with limestone.
The Ravenloft game setting's Van Richten's Guides not only expanded on a lot of creepy D&D monsters' powers, but also gave plenty of them unique Kryptonite Factors of their own. We're not talking about the usual garlic-vs-vampires stuff; in Ravenloft, even golems have their own personalized Kryptonite, which players have to figure out if they're going to use it against the baddies.
Vulnerability and Weakness are used to represent this in GURPS.
A rather spiteful example in Warhammer 40k with the Grey Knights Space Marines, MagitekSuper Soldiers that comprised the fighting arm of the Ordo Malleus, also called the Daemonhunters. Back in 3rd edition and earlier, Daemons were generally pretty rare but powerful shock troops that were small auxiliary subsets of other armies, like the Eldar with their Avatar and the Chaos Marines with their Chaos Daemons. One usually wouldn't fight an all-daemon army, and if an all-daemon army ever was fielded (usually by the Munchkin, given that this was a major Game Breaker back in the day), it usually was by the player's choice. So if you spammed Daemons and came up against a Daemonhunter player, you were just getting your well-deserved comeuppance for fielding a cheap army. But then Games Workshop went and split the Chaos Marines from the Chaos Daemons into two separate books in one of the most maligned decisions in the history of the hobby (which is saying a lot!), and suddenly you had an entire faction who fell prey to another army almost by virtue of the other army showing up.
As of April 2011, the Grey Knights themselves were given their own book to replace the Daemonhunters Codex. They're still insultingly effective against Daemons, if notmore so. They just got better against other armies.
Grey Knights have more or less became the Elite Mook of the Imperial forces, rather than a dedicated Daemonhunting branch. However they still have a horrendous number of special rules against Daemons and it's even possible to statistically destroy 33% of a Daemon player's army before the game even starts, and that's without tailoring. Before these rules came with an additional rule that benefitted Daemons, to balance out the power. It's gone now.
The official adventure module, Time of Crisis adds a weakness to the Big Bad Omega in the form of the cosmic detonator rods you've been pulling from the various Cosmic bombs which will completely bypass all of his defenses, potentially turning the final battle into a curb stomp.
Essentially required of characters (including NPC monsters) with superhuman toughness and/or regeneration in The Dresden Files. Something — referred to as "the catch" — must exist that bypasses their defenses, and common and/or obvious catches can provide point cost breaks. (Obscure ones like Nicodemus's vulnerability to his own Judas Noose are okay, too, it just means paying the full cost.)
Given the origin of the trope, pretty much any superhero RPG of course has a version of it. Champions for example provides both Vulnerability (where certain attacks are more effective) and Susceptibility (where just exposure to the offending factor is enough to cause ill effects), plus of course the option of applying Limitations to powers so they become cheaper but for example don't work under all circumstances or against certain things.
MMORPG Example: In City of Heroes, one can unlock the "Kheldian" Epic Archetype, a form of Energy Beings from outer space that have merged with humans. Though they possess a greater arsenal of powers than "ordinary" heroes, as well as the unique ability of shapeshifting, they also possess a fatal weakness to a particular form of Quantum Energy. Thus, while playing or teaming with one, enemies wielding Quantum Array Guns are mixed in randomly with the ordinary enemies — as are the lethal "Void Hunters", mercenaries specifically trained to hunt and kill Kheldians, adding implants that protect them from Kheldian attacks to their Quantum Array Guns.
This weakness was toned down due to years of player complaints as the Quantum Weapons were considered to be too commonplace for such a powerful attack. Now the quantum weapons deal less damage and only stun the player for a fraction of a second rather than taking over a third of their life and leaving them stunned for too long to defend themselves.
Having a Kheldian on the team will occasionally spawn Shadow Cysts that spawn spirits that ruin accuracy and attack speed of everyone on the team. Oh, and they explode when destroyed. And they're surrounded by Mooks who will probably kill you because you can't aim or fight back. For the most part, Shadow Cyst = Total Party Kill. Thanks Kheldians!
To add insult to injury, Kheldians aren't really particularly overpowered. They're actually pretty lackluster in comparison to the other archetypes, at least without a whole lot of work and expense tricking out your build.
Haar in Fire Emblem 10 is an otherwise One-Man Army mechanically, but (also mechanically) is pretty much always 2 hit killed by thunder mages.
This applies to almost every unit with a weakness in the Fire Emblem games: Attacks with an advantage do triple damage. And pray you don't get unlucky enough to get hit by a critical hit by your weakness
In Tears to Tiara and the sequel Tears to Tiara 2, non-humans on your team are effected whenever the bad guys use Obelisk to unleash the "holy" aura Gravitas.
Runescape lets you create Kryptonite in the form of Bane Ore. This stuff can be tuned to various creatures, and doing so will make it harmful to them. Bane Metal can then be made into arrows and bolts. Balmung, the axe you use to slay Dagganoths during a difficult quest, is revealed to be made of Bane Metal as well.
The Vampyre Quest series brings us Silverthril, an alloy of mithril and silver, which is somewhat effective at slaying immortal Vyrewatch. Later on, weapons crafted from the Blisterwood Tree take this Up to Eleven.
In Scribblenauts, a few creatures are impossible to kill except using some special objects:
Vampires can only be harmed by crosses, stakes, garlic, sunlight and anything with the adjective Holy. Using any of those will instantly slay the vampire (yes, even throwing a clove of garlic to him), but there are useless or very weak weapons against any other foe.
In the superhero spoof Adventure GameThe Frenetic Five versus Strum und Drang, the character Pastiche has various powers, the most notable of which is an ability to become an Intangible Man (woman). Her only weakness: she can't phase through rope.
In Tales of MU, the half-demon Mackenzie may be partially invulnerable, but crossing yourself is the only thing needed to repel her. In peoples of faith, this actually pushes her away and causes unbearable pain.
Incredibly powerful mage Fey in the Whateley Universe is indeed one of The Fair Folk, and so she has a weakness to cold iron. And synthetics, which give her really nasty rashes. She has wardrobe problems because of that one.
Played with by Phase, who's managed to slip a fake Kryptonite Factor into her official file. For the record, it's "dark chocolate administered orally".
Upon entering melee range of any anti-dragon Noble Phantasm, Uther from Fate Nuovo Guerra suffers a rank-down for all of his stats, in addition to any damage bonuses they have against him.
Fidget, a Kid Hero speedster from the Global Guardians PBEM Universe, takes actual physical damage if you tie him down and prevent him from moving. If you stop him from moving, his power literally builds up and starts vibrating his cells to pieces.
Interestingly, in Superman: The Animated Series, it was originally planned that Supergirl, being in this iteration not from Krypton, but rather the sister-planet of Argos, would not have a weakness to Kryptonite. By the time of Justice League Unlimited, though, the weakness was firmly in place.
Spoofed in an episode of Freakazoid!, in which bad guy Guttierez tries presenting a variety of weaknesses (the color yellow, water, and kryptonite itself), failing each time, as Freakazoid points out that that's some other iconic character's weakness.
Freakazoid himself has two rather obscure and ridiculous weaknesses, though: he can be imprisoned in a cage with graphite bars charged with negative ions, and he has an aversion to "poo gas".
Freakazoid: Dumb, dumb, dumb! Never tell the villain how to trap you in a cage! Guttierez: You probably shouldn't have helped us build it, either. Freakazoid: I know! Dumb!
Though as Guttierez pointed out, no one likes "poo gas".
Captain Planet has a very odd weakness in that it's pollution, the very thing he's trying to fight. It'd be like Superman deciding to specialize solely on kryptonite cleanup duty.
His Evil Counterpart Captain Pollution, is weak against pure wind, water, earth, and fire while being composed of concentrated pollution. This makes it interesting in that they're literally walking kryptonite to one another.
Captain Planet was also shown to be weak to intense hatred in at least one episode. Adolf Hitler managed to completely disable him just by glaring at him. However, hate is regularly shown to be the pollution for Heart as even one of the rings used to summon Captain Pollution was Hate which was the negative copy of the Heart ring.
In a Bad Future segment on The Grim Adventures of Billy & Mandy, rebels led by Irwin use frogs as weapons, as they've learned that they are giant worm/planetary tyrant Future Mandy's Kryptonite Factor. They're wrong, as Mandy had leaked that information herself.
In an episode of Tiny Toon Adventures spoofing the Superman movies, "Super-Babs" was weak to carrot cake — she couldn't stop eating it, and the villain continued feeding it to her until she was too overweight to fly after him.
The Justice League cartoon downplayed or ignored the Kryptonite Factor of every character except Superman. Green Lantern's vulnerability to yellow was never actually mentioned (though occasionally, if you watch closely, you'll see yellow stuff getting through his force barricades). J'onn J'onnz had no particular vulnerability or phobia regarding fire (though he had a bad case of The Worf Effect in the first season, and he would occasionally struggle in situations where there was a lot of fire). Aquaman never seemed overly discomfited by being out of water for extended periods. Wonder Woman... well, she'd lost most of her Kryptonite Factors by the time the series started anyway. Hawkgirl eventually gained a Kryptonite Factor that was more emotional than physical and ended up resolved by series end anyway. The Flash almost never used his powers to their full extent (not unlike Superman), with the idea that he never really pushed himself to excel...and when he did, he was given a convenient excuse not to again. Batman's "Kryptonite Factor"—that he was a perfectly mortal human—came up time and again, but, being Batman, doesn't really count.
When Lex Luthor was in the body of The Flash ("The Great Brain Robbery"), he took down Green Lantern with a cup of (yellow) pudding.
Fair enough, though, they used the weaknesses against Amazo, particularly Kryptonite.
Heroes actually abused this, by having Martian Manhunter pretend to be Superman in front of Lex Luther to get a confession for a crime.
The ThunderCats are vulnerable to "thundranium", a rare mineral that is pretty much a poorly-disguised knock-off of kryptonite.
In the Teen Titans cartoon, Starfire is allergic to metallic chromium. The allergy is more dangerous to others than herself, as it causes her to sneeze energy blasts. It even turns out to be an advantage, as it allows the team to track a chromium-based bomb. It's also a big case of artistic license, as chromium is used in a lot of common technologies.
Imaginary Man, a superhero imaginary friend on Foster's Home for Imaginary Friends, is weakened by girly things, particularly flowers. Similarly, his evil nemesis Nemesis, loses her powers whenever her hair is messed up. It later turns out they were thought up by a boy and his sister, respectively, just to annoy each other.
The Sushi Pack are weakened by heat, and since they have a tendency to announce it, their most recurrent villains usually keep a couple of heat lamps around.
On The Mighty B!, Bessie (who fancied herself a would-be superhero) once tried to find her Kryptonite Factor by going through every food item she could think of alphabetically. By the time she got to zucchini she was so full that she became violently ill, and thus thought that zucchini was her weakness.
In The Powerpuff Girls the titular girls lose their powers if they come in contact with Antidote X.
On Batman: The Brave and the Bold, when Batman received powers on the planet Zur-En-Arrh, the supervillain Rothul quickly figures out the new Superman-like Batman's weakness: Quartz.
Parodied in a Robot Chicken sketch when after a fireball destroys another enemy, it also melts half of Composite Santa's body.
Composite Santa: Temperatures over 32 degrees Fahrenheit! My only weakness!
The animated film Superman: Doomsday contains an almost amusing example in that even Superman needed Kryptonite to defeat his clone with identical powers. Admittedly, the real Superman isn't quite at full strength at this point.
Superman: You have all my strengths... and weaknesses.
Specifically parodied in one episode of the Earthworm Jim animated series. Jim is helpless against the substance known as Wormtonite (which Peter Puppy claims they found at the back of the fridge, and might once have been cheese). Bizarrely, its effects include turning Jim into a bowl of candied corn.
Spider-Man would occasionally make sly references to a "guy who's allergic to green rocks".
Haggarium drains the power of Voltron in Voltron Force, as well as its component lions.
The Simpsons: Bart once discovered principal Skinner's allergy to peanuts, and used it to practically enslave him. Skinner soon learns that Bart has an allergy too; Shrimp. They end up in a "sword" fight with sticks with their opponent's kryptonite on the end.
Danny Phantom is weakened by a flower called Blood Blossom. It removes his powers while causing him extreme pain. That's not to mention the various weapons his parents and Vlad have devised that can remove his powers or hurt him while he is intangible.
Ectoranium, introduced in ther Series Finale, is a green glowing rock that ghosts can't touch without being painfully shocked; they can still phase through it, which is an important plot point. Kind of an obvious Expy of Kryptonite, but in this case the Ectoranium is as much of a danger to humans as ghosts since it's a large asteroid that got knocked off course towards Earth.
WordGirl loses her powers and gift of perfect vocabulary when exposed to lexonite, a radioactive mineral from her home planet.
The 1987 version of Teenage Mutant Ninja Turtles parodied this in the episode "Michelangelo Meets Bug Man". In it, Michelangelo finds Bug Man, who turned into the superhero when he got angry, wrapped in chains that were laced with his main weakness before being thrown down into the sewer. His weakness? "Leestanite"! note The name is not an accident: it was a play on famous comic book creator Stan Lee.
While it is much less known, chocolate is dangerous for cats too, though cats are much less likely to eat it than dogs are.
Any human with a severe food allergy. Peanuts are a frequent culprit here, with some unlucky folks unable to be in the same room as peanut products without going into respiratory shock.
Salt to snails/slugs.
Freshwater fish in saltwater and vice versa due to osmosis.
The New England Patriots and Bernard Pollard. Pollard has destroyed the Patriots so many times that his fan nickname is the "Anti Patriot" and the "Patriot Killer". Pollard is a good player and is generally well-regarded, but it's bizarre coincidence that Pollard has done the biggest damage to the Patriots.