The Safeguard from Blame! don't want to kill all humans, per se - Only the ones without an incredibly rare and possibly extinct genetic marker. Kill 99.99999% of all humans would be more accurate.
In Knights Of Sidonia by the same author, the Gauna appear to have the extermination of humanity as their goal.
Michel in Mermaid Melody Pichi Pichi Pitch wants to kill all the humans. He doesn't know why, except that he thinks it's a divine order; however, another part of this supposedly divine order is to turn the world into a creepy wasteland with flying fish and DNA strands shooting out of the sky. This should tip you off to its suspect nature already, although he doesn't get it until he is rejected and the truth revealed.
Michio Yuki in MW wants to kill every human, including himself, with the titular chemical warfare. He forms this because MW is affecting both of his brain and heart.
The titular creatures of the manga series Parasyte. They're perfectly capable of surviving on normal foods, but have an instinctive compulsion to kill & eat humans, preferably in the most grotesque way possible. Most characters come to the conclusion that they were created by Mother Earth herself to save the environment by culling the human population. This ultimately fails, as the Parasytes gradually acclimate to human society and become indistinguishable from ordinary humans.
Kyuutarou Ooba in Kemonozume hatches a grandiose plot to make everyone on Earth revert to monsters and eat each other for...some reason that's never fully explained. Is he doing it for his often-teased son? Is he doing it to improve the world? Is he doing it just for giggles? Whatever the case, he explains his agenda pretty thoroughly while riding a giant sphere full of poison gas into a major city:
Ooba: Die! Die! Everybody die! Those who kill, pick on others, act like idiots! The mean, the petty, the calculating, the cowardly pacifists, the warmongers, everybody DIIIIIE!
Lance from Pokémon Special harbors an intense hatred for his own species, due to his Viridian-granted power to hear the thoughts and sense the emotions of Pokémon, twisted by his memories of wild Pokémon dying slowly in pools of industrial toxins. His grandiose scheme in the Yellow saga is to unleash an army of Dragons on the human population, creating a utopia for Pokémon...creepy.
Mewtwo, in the anime, has much the same plan before the end of Pokémon: The First Movie. He rather effortlessly starts a storm that will grow and grow until killing all humanity and, as it happens, all Pokémon who aren't clones. Which is like, 20 out of nearly 700 species nowadays. Yeah, he was a little angry at humanity that day.
Neon Genesis Evangelion shows us a careful balance between this and Assimilation Plot. If humans trigger Instrumentality, everyone will lose individuality and become one with each other. If the Angels do it, it will repeat Second Impact and completely wipe out humanity (or at least that's the justification of killing all 15 of them).
Hao, the Big Bad of Shaman King, is a shaman capable of mastering all the elements of the world and is even capable of surviving in molten lava. Since he knows that normal humans cannot do everything that he can, he decides to Kill All Humans only because he believes that they are a threat to the planet, so he can build his own shaman-only kingdom. He believes that the Great Spirits possess the power that will help him cleanse the world of all humanity.
Hao: (referring to the power of the Great Spirits) I've been waiting a thousand years for this power. The power that will WIPE humanity from the FACE of the planet!
In Monster Johann Liebert's ultimate objective is to destroy humanity and be the last human on the earth.
The goal of Fiamma of the Right from To Aru Majutsu no Index, claiming humanity is too sinful to be redeemed. Touma eventually defeats him and convinces him to travel the world and reconnect with humanity. Touma realized that Fiamma was a guy who wanted to save the world, but lost sight of the people in front of him along the way.
Master Asia was also this way as well. Disenchanted with the world due to the fact that the Gundam Fight constantly ravages the planet every four years, he decides that humanity should be eradicated so nature can be restored to its natural beauty and joins the Devil Gundam. However, in his final fight with Domon, he comes to realize that humanity is as part of the world as is nature, and he relents in his mission.
The Titans of Attack on Titan seem to have an instinctive desire to eat humans. Since they lack a digestive tract and draw energy from the sun, there doesn't seem to be any reason for their obsession with munching on the human race. As a result, the human race was devoured to the brink of extinction and the survivors have spent the last century sheltered by massive Walls. Then there's the mysterious Colossal Titan and Armored Titan, which seem to exist solely to destroy the Walls and ring the dinner bell for their regular, mindless kin. It's unclear whether the extermination of mankind is their group's true goal, or was merely a means to further some other goal.
Later in the series, one character asserts that Titans aren't actually seeking to kill humans. They've always sought to eat them, meaning when a Titan appears that is pointedly killing people without trying to eat them, something is very wrong. Even later it's indicated that Titans were once humans themselves and can regain a measure of their humanity by eating a Titan Shifter. Whether Titans are instinctively aware of this, which is why they eat humans, or it happens completely incidentally while Titans eat humans for some other reason is unknown.
Super Buu does this as a throwaway in Dragon Ball Z. Piccolo reminds him that he said he'd kill everyone on Earth before fighting the Z Warriors (Piccolo does so not out of raw stupidity, but because their side needs time to recuperate; besides, they have the Dragon Balls to wish everyone back to life). Super Buu's response: the Human Extinction Attack. Exactly What It Says on the Tin.
This is actually what Goku was originally sent to Earth to do. Good thing he bumped his head and forgot about it. Raditz tries to remind him, and then when he realizes he isn't listening, plans to do it himself. So do Nappa and Vegeta. Freeza and King Cold also were planning this before being stopped by Trunks. Same with the androids, Cell... well actually pretty much every DBZ villain.
Onslaught in the Marvel Universe started out as a harsher version of Magneto, but then Professor X's arguments about mutant/muggle equality led it to the same epiphany as Sweeney Todd, minus the awesome music or pie shop.
The Sentinels occasionally fall into this trope. Originally they were programmed with two directives; 1) neutralize mutants and 2) protect human life from mutants. Occasionally some Sentinels will logically deduce that, since all organic life has the potential to mutate, the only way to fully neutralize all mutant life is to eliminate all humans.
While at other times, Sentinels are bad for humans without actually being homicidal; they merely reason that they can best protect human life by ruling it.
Lady Death, from the Evil Ernie comics and some sequels. She can't come back to earth until there are no more people alive on it.
In Judge Dredd, the Dark Judges seek to annihilate the living because life is illegal on their world (and they don't acknowledge jurisdictional boundaries). Judge Death (real name Sidney) was a born sadist and psychopath, whose antics as a child include throwing his dog over a cliff after he was reprimanded for torturing it, setting some sort of horrible alien thing (like the bastard lovechild of a tarantula and an octopus) on his sleeping sister for reporting his psychotic behavior, implicitly causing her to be paralyzed for the rest of her life from its poison, and throwing the switch personally when his father was sent to the electric chair. He was also the one who sent his father to the chair, having already learned plenty of life lessons from him (his father was a Depraved Dentist) and realising that not only was his old man starting to kill more often, he himself would be caught if he didn't send him to prison first. Using this to get a career in his world's equivalent of the Judges, his diseased brain came to the conclusion that, as only living people commit crimes, life itself should be made illegal and punished by 'cleansing'. With the aid of two cannibal demon-witches and three almost as deranged followers, he transforms into an undead abomination and sets out exterminating all life in existence. Or, in simpler terms, the Dark Judges occupy a twisted border between Knight Templar and Omnicidal Maniac.
Ultron's second attempt at a mate (and third or so attempt at a good Dragon), Alkhema, split with Ultron because they disagreed on procedure: Ultron wants to Kill All Humans by efficient, genocidal means, while Alkhema wants to take her time and enjoy the process of killing by hand.
Commander Blanx and Malefic in Martian Manhunter were Mars' equivalent of this, exterminating all the Martians.
The Xorda in Archie Comics' Sonic the Hedgehog, mostly because the military killed and dissected their ambassador. When they came back and found Mobians in their place, they decided to do it again, deeming Mobians just the same as humans.
In the 2007 Transformers movie, inanimate objects brought to life by the All Spark immediately set about wreaking death and destruction. This is just about excusable in the case of the mobile phone, since it was trapped, but do vending machines and X-Boxes really harbour a secret desire to Kill All Humans?
The going theory is that the newly-created robots weren't so much evil as feral.
Agent Simmons mentions that all modern technology has been reverse engineered from Megatron/NBE-1. Since this means these objects are essentially descendant from him, it's only natural they be evil as well.
Subverted with Godzilla. In Ghidorah The Three Headed Monster he reveals that he hates humans for "bullying" him, apparently having perceived the H-bomb tests that destroyed his home and food supply as an unprovoked attack. Eventually he becomes a hero, not out of any obligation to mankind, but to protect the earth, which Godzilla begrudgingly comes to accept the human race as being part of. Adopting a son and developing allies among the other monsters of earth provided further incentive for him to become a protector rather than a destroyer.
Played straight by many of Godzilla's opponents, most notably King Ghidorah, an omnicidal space monster who destroys entire planets.
In Godzilla Final Wars in which a young boy asks his grandpa why Godzilla is destroying a city. The grandfather tells the boy it's because Godzilla is angry at humanity for making the nuclear bomb in the first place.
The film Godzilla, Mothra, King Ghidorah: Giant Monsters All-Out Attack! takes this even further and states that Godzilla wants to wipe out everyone in Japan (and possibly the rest of the world). It turns out he's being driven by the vengeful souls of those who died in WWII who have been forgotten by the Japanese.
The Godzilla of Godzilla 2000 doesn't seem particularly interested in killing humans for the sake of it, but he also doesn't take any special effort to save them. He's more interested in getting revenge on Orga.
In Daybreakers, humanity has been replaced by a vampire society, who have hunted the remaining humans to almost complete extinction to serve as their food source. The vamps apparently didn't think far enough ahead to realize that they set up an unsustainable food chain by killing all the prey and not allowing their numbers a chance to recover while also maintaining no population regulation of the predators.
Oblivion (2013) : One of "Sally"'s goals is eradicating the last surviving pockets of humanity.
While not particularly harmful, the insects called snow gnats from A Series of Unfortunate Events sting humans just for the fun of it. Klaus does state, though, that they are mildly poisonous and a large enough number of stings could cause severe illness.
The Ryall from Antares believe that it is impossible for two sentient species to coexist, so they save time by attempting to exterminate the humans on contact.
The Auditors of the Discworld want to do this. They find life messy and unpredictable (they prefer a deterministic, Newtonian universe) and humans the worst of all.
Star TrekGreater Than the Sum: "We are the Borg. You will be annihilated. Your biological and technological distinctiveness have become irrelevant. Resistance is futile...but welcome."
While most of H.P. Lovecraft's deities would destroy humanity without really paying attention, Nyarlathotep seem to be bent on killing all humans (or rather, getting us kill ourselves). Why? I don't know, guess he's just being a dick.
In Lester del Rey's "For I Am a Jealous People!", aliens arrive without warning and just start killing all humans. One man finds out why, it seems that God (yes, the Jewish, Christian, Islamic one) has decided that humans are no longer his chosen people and the aliens now are. So he ordered them to kill us all off.
Stalker Fang: "... humanity is a plague; a swarm of clever monkeys which the good earth cannot support. All human civilizations fall, Tom, and all for the same reason; humans are too greedy. It is time to put an end to them forever."
This is basically the whole plot of Charles Pellegrino and George Zebrowski's The Killing Star. We start with planet-busting kinetic weapons hitting all human colonies throughout the solar system at 92% of the speed of light. The few survivors are then hunted to extinction. Why? Humans are dangerous. I mean, have you seen the things we do to each other on TV?
In Thomas Disch's The Genocides, alien invaders turn the Earth into a giant monoculture for their own crops, and seek to wipe out annoying pest species such as humans. They succeed.
This is the plan of the Neanderthals in The Extinction Gambit, the first novel of The Extraordinaires.
This doesn't actually end up happening, but it is mentioned that some of the Galactics in the Uplift Universe wanted to do this at First Contact, on account of past ecological mismanagement. However, between humanity having tried to clean up its act and its actual patronage of two species (dolphins and chimps), the Galactics grudgingly decide that they are bound not only to let us live, but also to allow us to colonize planets (which patron species are entitled to do).
Mystery Science Theater 3000. Crow and Tom sometimes veer into this territory, and the one time Mike attempted to build a robot... did not go well.
Alien races and robots are particularly volatile. The Cylons from the original Battlestar Galactica were out to destroy all organic life; they'd wiped out the original reptilian Cylons who'd created them and then went after humans. ("War of the Gods" revealed that they were programmed to do so by an entity that was basically Satan.) The Cylons in the new series still have killing all humans as their initial goal, but the series expands on their reasons, and as they developed and began to show more individuality they wavered between this and helping the humans (with help being occupying them and ruling by force) with alarming suddenness. Frakkin' Toasters.
The original series stated that the Colonials interfered in the Cylons' conquest of another race, sparking off a thousand yahren war.
The Daleks in Doctor Who want to EX-TER-MI-NATE anything that isn't a Dalek.
And the Silurians want to Kill All Humans to reclaim the Earth, which they ruled in the Eocene period. Same with their aquatic relatives, the Sea Devils.
The Cybermen are a slight variation, merely wanting to convert all humans into Cybermen.
In "The Power of Three", the Shakri want to Kill All Humans to prevent the human plague from spreading throughout the galaxy.
The Judge deserves particular mention, since his only reason for existing is to burn the humanity out of humans and "corrupted" demons like vampires.
On Lexx, His Divine Shadow, who wanted to destroy all of mankind to avenge an ancient grudge. The second season's Big Bad sought to take the concept yet further by converting all matter in the universe in its image. The series being what it was, both largely succeeded.
British Sci-fi sitcom Hyperdrive had a hilarious song Kill The Humans which can be heard here.
One of the major backstory elements in Babylon 5 is a disastrous war between the Humans and the Minbari. The Minbari are first introduced as a race of spiritual scholars, but those are just one of the races hats. Another major faction are Proud Warrior Race Guys who have one of the most advanced and powerful space navies in the galaxy and faught with no less than the annihilation of the entire human race as their goal. However, it's later revealed that they just fought because that's what they do. The order to exterminate humanity was in fact given by a high ranking priest when the highest religious leader was accidentally killed by humans.
Adam's goal in the second season of Heroes is to unleash the Shanti Virus and kill 99.93% of the human population because people suck.
Helen Cutter in Primeval also decides that Humans Are the Real Monsters and goes back in time to prevent humanity's evolution altogether. It's pointed out that her actions will also erase her from existence, but apparently she doesn't care.
Star Trek: Enterprise. As part of a Batman Gambit, the Spherebuilders convince the Xindi that humanity will destroy their homeworld in the future, so they decide to destroy Earth first. An alternate timeline shows them going to the trouble of tracking down and destroying human colonies even after Earth is destroyed. This is somewhat reasonable, as expecting humans to not want vengeance after Earth is destroyed would be the height of silliness.
Nick Cave and the Bad Seeds' "The Curse Of Millhaven" shows Loretta's philosophy falls into this category: "Lalalala, lalalalie/ All God's children have all gotta die."
In Queensr˙che's "Nm 156", a governing supercomputer opts to annihilate humans, not because Humans Are the Real Monsters, but because it's been tasked to enforce a stable social order, and humans are unpredictable. Ergo, "Social control requires population termination."
Virtually the entirety of Mayhem's fourth album Ordo Ad Chao consists of this.
Well I've had enough of all your pretty pretty speeches
Receive your punishment, Expose your throats to my righteous claws
And let the blood flow, and let the blood flow, flow, flow, flow
Space 1889 Ground cleansers want to kill all humans on Mars. Cult of the Worm want the entire planet to die, including themselves.
The ultimate goal of the Dark in earlier editions of Nobilis was to encourage humanity to kill itself. The justifications they gave ranged from "Earth would be better off without them" to something about suicide being the time at which you have the most control over your life, since nothing after you pull the trigger can influence you. This has been toned down somewhat.
Warhammer 40K has pretty much everything trying to kill humans. To be fair, humans are trying to kill everything back.
In the backstory of Guilty Gear, the Gears wanted to obliterate humanity. They lost the war, but a few decades later one of them, Testament, decided to wake up Justice (one of the strongest Command Gears) and restart the process. Testament still isn't fond of humans in the later games; in one of his endings in Guilty Gear XX, Dizzy is killed by I-No, at which point Testament gives up on the human race, murders Johnny and any of the Jellyfish Pirates he can get his hands on, and goes right back out to trying to render humans extinct.
In Chrono Trigger, an optional sidequest in 2300 A.D. involves an artificial intelligence with a robot army that wants to kill all the humans to "end their suffering". Given that the humans in this case are immortal and live in a foodless post-apocalyptic wasteland, it would actually be the nice thing to do.
Towards the end of Ninja Gaiden 3, Clancy gets transformed into a super being in the subspace and tells Ryu that in order to protect the Earth, he must Kill All Humans. He tries to convince Ryu to join his side, but everyone knows the answer to that.
Alex Mercer from Prototypewhile still being alive, released a super-powerful mutated virus that would consume all of humanity in a matter of months. Thankfully, the virus that consumed him managed to stop it.
The Phoenix Group in Rainbow Six plots to wipe out humankind with a genetically engineered strain of Ebola.
Galerians is a pretty textbook example of the 'sentient computer' version.
Also the goal of Viridi upon her debut in the sequel. She already had problems with Mankind for the typical reasons, but it finally comes to a boiling point when Hades tricks the humans into warring with and slaughtering each other over a wish-granting item... That isn't real. To be fair, though, the humans don't know the item is fake.
The Big Bads in Mass Effect series, the Reapers. Well, that, or turn them all into a new Reaper - that also involves killing them first, though.
Purple Eyes's new philosophy after his initial defeat in Pokémon Ranger Guardian Signs. He tried to convince the Creator of all Pokémon to go along with it, for Arceus's sake!
In DEFCON, a global thermonuclear war simulator, the Genocide mode gives the player a point for every million enemy civilians they kill. Your own civilian losses are irrelevant. Your only goal is to ensure that the communists/capitalists/whatever die in a nuclear fire. It's possible to win the game even while nuking your own population centers.
In the Halo series, the Covenant, the main enemies most of the time, are on a religious crusade throughout the galaxy and their leaders, the three Prophet Hierarchs, have declared humans a heretic species when they discovered that they are called Reclaimers by a Forerunner A.I., and the revelation of this would shatter their rule.
Yurt in Demon's Souls has the goal of killing every living human in Boletaria. If you unlock his cage and don't attack him he will come to the Nexus where he continues to secretly murder the NPCs while you're away. This can result in being unable to learn any new spells, since the spell trainers are dead. It's not just combat in this game that is unforgivingly cruel.
The Thalmor of The Elder Scrolls V: Skyrim. Their ultimate goal is to dismantle reality itself and ascend to godhood, and one of the major obstacles to this end is humanity. They don't want to just kill all humans, they want to kill the very idea of humans.
In the Diablo III expansion, Reaper of Souls, Malthael and his Reapers want to exterminate humanity due to their origins as the offspring of angels and demons, the latter of whom the angels absolutely hate.
In Sluggy Freelance the Dimension of Pain demons are bent on killing all humans, largely because they've got nothing better to do. Played for irony, since we've been shown that, if they do wipe out all humans in a dimension, they then get bored since there's no one around to torture and kill anymore.
Coyote: Renard loooves humans! Not like Ysengrin, who would kill the lot of them, given the chance.
Possibly lampshaded in The Order of the Stick, in which Redcloak (a goblin) summons a Chlorine Elemental and instructs it to kill all the humans nearby. The elemental floats off mumbling, "Kill All Humans".
Tsukiko: And then he ordered his elemental to try and kill me!
Xykon: Redcloak, is this true?
Redcloak: No. Technically, I just ordered the elemental to kill all humans, and then "forgot" to make an exception for her.
The civilized monsters of RPG World exhibit this trope whenever there's the equivalent of an international incident... other reasons too. They're pretty touchy. Good thing they stick to holding up placards and shouting and televised news reports.
Parodied in thisSaturday Morning Breakfast Cereal strip. When robots gain sentience the human immediately assumes that they are going to decide to kill all humans, the robots are so shocked to learn that humans think this way that they decide to kill all humans.
Parodied in this video When a hacker augments his Kinect to make it self aware.
Subverted in Futurama, where Bender (and it seems, many robots) have a suppressed desire to kill all humans, but they don't actually do it. Unless Mom orders them to do so.
Bender:(sleep-talking) Kill all humans... kill all humans... must kill all... Fry: Bender, wake up! Bender:(yawns) I was having the most wonderful dream. I think you were in it. ... [falls asleep again] Bender: Hey, sexy mama... wanna kill all humans?
This is subverted even further when, in one episode, it is revealed that Bender would always whisper "except one" after he said this. Fry was that one.note Though this was during a very Mind Screw-y episode that left the viewer with a metric ton of misdirection and questionable reality so it's impossible to know if this is how Bender really feels.
After Hermes accompanied Bender on his quest to find "Inspector 5," Bender announced he was placing Hermes on the "Do not kill" list. Which, we can assume, consists of exactly two names at this point.
And played straight when the crew has to deliver a packet to a planet inhabited by Killer Robots. Turns out the reason for this is largely propaganda by the robot elders, blaming humans for their society's shortcomings, as well as portraying humans as something of a cross between vampires and zombies.
And played straight one more time in the original what-if-machine episode. Bender asks, what if I was a giant robot? You guessed it.
Bender: I came to Earth with a simple dream: To kill all humans. And this is how it must end!? Who's the real 600 ton giant monster here? Not I... Not... I...
In one of the movies, Bender joins a secret society of robots bent on killing all humans, only to find that they've grown soft over the years and just hang around drinking. According to Hedonismbot, "We haven't killed a human in over 800 years, and that was a very sick Girl Scout."
Demona on Gargoyles was often plotting this, which lead to many humans hating the Gargoyles, which makes her original hatred seem justified...it's an ironic vicious circle she finds herself trapped in. Particularly once she starts becoming a human rather than stone during the day.
In The Grim Adventures of Billy & Mandy, Billy's greatest fear is clowns, believing that they will one day rise up and "DESTROY US ALL!! DESTROY US ALL!! DESTROY US ALL!! DESTROY US ALL!! DESTROY US ALL!!"
DESTROY US ALL!! DESTROY US ALL!! DESTROY US ALL!!
Spoofed in at least one episode of The Simpsons: A robot is brought in to show to Bart's class. When Bart spots the man operating the robot in a tree outside, he knocks him out with a rock. The robot then slumps for a second, before rising and declaring "Command link severed. Default mode: Crush. Kill. Destroy!."
Also spoofed in South Park. Chef is trying to figure out the remote control for his spiffy new TV and activates "HEM" without knowing what it is. The TV sprouts arms, legs and lasers and goes on a bloody rampage in "Human Eradication Mode."
Spoofed yet more in Family Guy. During the episode where Stewie becomes obsessed with Miley Cyrus, it turns out she's actually a robot created by Disney's Imagineers to be the next massive brand name to sell to teenage kids. When this is discovered Stewie is shocked, while Brian is intirgued, wanting some 'quality time' with the Cyrus-bot. Long story short, he accidentally switches her mode with a stupid-in-hindsight button that turns her default setting to killing all humans. A King Kong parody with Peter and Quagmire in a biplane follows.