The Anti Spirals from Tengen Toppa Gurren Lagann wait around watching to make sure the universe doesn't develop too many intelligent beings capable of creating or controlling spiral energy, including humans. Once they decide there are too many, they sweep in and Kill 'em All . They do it with a really snotty attitude, too, which adds insult to injury.
The Super-Paleolithic People (Choukodaijomonjin) from Gekiganger 3.
The Dark Kingdom and Dead Moon Kingdom from Sailor Moon.
At the smallest end of the scale, Rozen from Rozen Maiden. He created a race of thinking, sentient creatures, made them blindly loyal, and commanded them to fight to the death until only one survives. Why? To earn his love. Only centuries later, after a pretender triggers a fake Alice Game, does he deign to show his face again ... to restore the status quo and reset the game back to start. With a grudging admission that "there are other ways to win besides battle." On the other hand, can a force, however mysterious, who creates a "race" with less than ten members really be considered a Precursor?
The Mu of RahXephon, a race of blue-blooded humans who vanished off the Earth several ten thousands of years ago due to one of their own experiments failing (the reason for said experiment? The scientist just wanted to see if it would actually work). The story happens when they try to come back, and the end of the series makes it very clear that they could effortlessly wipe out humanity if they really wanted. They don't, they only suppress the TERRA organization that is directly opposing them. Their real goal is to re-do that aforementioned failed experiment properly and Ret Gone the entire human race, so that they can have Earth for themselves. Oh, and the Humongous Mecha they use are Powered by a Forsaken Child, meaning that every Dolem killed was an innocent human life suddenly ending.
Except for those few like Largo which were powered by knowledgeable Mulians.
The case of Humanity vs Nausicań of the Valley of the Wind has been opened. It engineered a vast, vast number of Weapons Of Mass Destruction, which include the titanic cyborg-like God Warriors, destroyed the entire ecosystem of the whole world, and finally all but perished in the Seven Days Of Fire. But its greatest sin was to create the Heart of Shuwa, a biological computer which contains a human-like consciousness, and which, when found by the few surviving humans, dispensed just enough scientific knowledge to enthrall them. Additionally, war technology pre-Seven Days Of Fire is still scattered across the planet, including the aforementioned God Warriors. And if that's not all, the Heart deliberately created the Sea of Corruption and the Ohmu to cleanse the planet, so its creators could live again in a purified world — after willingly destroying the current mankind.
The Celestials in Earth X created superheroes in order to act as an "immune system" against Galactus, in order for the baby Celestial gestating in the Earth's core to come to maturity. The thing is, when it matures, we die. We'd die sooner if the Earth was eaten by Galactus.
Emotionally lobotomized a former member of their own collective, Ganthet, who had previously been expelled from the Guardian Council, went on to found the Blue Lantern Corps and ultimately returned as a serving Green Lantern.
Determined that the Green Lantern Corps is too unstable, and indeed, free will itself is a threat to the stability of the universe. As a result they have unleashed a "Third Army", which consisted of an endlessly self-replicating totally emotionless power suit that takes control of its victims while keeping them totally conscious, with the intent, either explicit or implicit, of eradicating all life.
Try to have Guy Gardner murdered by said army, and when he survives, frame him for the deaths caused by the attack and expel him from the Corps.
Your honor, we would like to bring forth a case against New Gods of the 4th world. Obviously, Apokolips and the various forces thereof, are guilty of this, but the prosecution argues that New Genesis is also guilty due to not taking precautions against Darkseid or cleaning up left over technology left behind on Earth. Furthermore, Metron's research into boom tube technology directly endangered the main DCU by making a battleground for these two forces. The prosecution asks for either a ruling or the case to be referred to the court for neglectful pre-cursors.
The unknown alien species from Supernova is smart enough to be able to encase "9th dimensional matter in a 3rd dimensional shell". This shell's energy has the effect of a Fountain of Youth when touched. (Better than candy!) The real use for this artifact? To blow up any civilization advanced enough to have developed star drive and reach the places where they've hidden these supernova causing weapons.
In Prometheus the Engineers/"Space Jockeys" were the advanced alien race responsible for seeding life on Earth. When one is awakened from stasis he immediately tries to destroy humanity.
The "Firstborn" featured in Sir Arthur C. Clarke's Time Odyssey and Space Odyssey books are pretty much Ur examples for both this trope andBenevolent Precursors respectively. In Space Odyssey they are super-advanced aliens that made it their purpose to promote the development of intelligent life throughout the Galaxy. After they moved on, they left their "Monoliths" to continue their work in their stead. In Time Odyssey they are the exact opposite: to them, intelligent life is indeed a treasure, but not one greater than their own existence. Every intelligent race out there, if left unchecked, would speed up the Universe's Heat Death, leading to their own extinction as well. The Monoliths are replaced with "Eyes", which act as observers and enforcers of their will; if the Firstborn's first plan to sterilize Earth with a massive solar flare 2000 years in the making failed, the Eyes can also double as planet-busting Q-bombs.
The Thrint in Larry Niven's World of Ptavvs. When their empire was threatened by a successful slave revolt, they went out in a blaze of spite, sending a telepathic blast that killed almost every intelligent being in the entire galaxy - including themselves. It took a billion years for sentient life to evolve again.
One story suggests they were not only abusive back then, but they also wanted to make sure they would get any pockets hiding for a thousand or million years after. This weapon exists until the modern day, and goes off from time to time, no longer able to kill all vertebrates, just anything that is sentient... The Thrint were notoriously stupid- they relied on mindslaves for any task requiring much thought or effort. They were about as emotionally mature as you would expect from someone waited on hand and foot since birth by entire planets, too, explaining the vindictiveness.
Also humanity's ancestral Ancient Astronauts, the Pak, who would kill us all if they met us today; a fleet had to be sent out to head them off and wipe them out before they could realize what had happened to us. They're violently xenophobic, and we've mutated far too much to smell right, and our culture is too different for them to accept.
Imaginatively known as "The Builders". It was shown that they made them to defeat another alien race and things went wrong. So less abusive and more technology has turned against us. Given the kitbashed and divergent technologies of Berzerkers over the millennia of endless killing, it in unknown if one race used them as the Final Option against another or if two or more different factions or races deployed these death machines against each other. (You could always ask a berserker—but they don't care, and you wouldn't survive to share the answer...) No matter how you slice it, Berserkers are shining examples of Horribly Right as well as contenders for largest mass production Precursor Killer models.
The gods in the Dragaera universe are ascended humans. They are not very nice people, but most of their manipulations on the material plane are for the sole purpose of preventing their old masters (the Jenoine) from coming back and enslaving the world to experiment on it again.
The Wolves/Inhibitors from Alastair Reynolds' Revelation Space novels seem to be this. They deliberately transformed themselves into (usually) nonsentient machines which act to prevent sentient life from spreading through the galaxy—typically by way of genocide, though they're sometimes willing to overlook planetbound life-forms. They do have a noble-sounding motivation—they're trying to ensure the collision with the Andromeda Galaxy doesn't wipe out intelligence permanently, and don't believe a multiple-species society can pull together to prevent the chaos ahead—but they've been slaughtering for billions of years, there are billions more to go, and it's questionable whether they really intended to end up this way.
Some of the shrouders are pretty abusive too; the one time they didn't kill or drive insane any human that got too close to their territory, it was part of a plan to trick humans into awakening the Inhibitors, so that the shrouders would know whether it was safe to come out of hiding. It wasn't safe, and humans were driven nearly to extinction as a result.
The Aldenata from John Ringo's Legacy of the Aldenata, with new abuses added with every new novel. Some are negligent, some are abusive. They took the Space Elves and made them unable to kill, but did nothing to their instincts to dominate and control, so instead they seek economic domination of everyone. They convinced most of the other races if they wish to ascend they have to be Perfect Pacifist People, knowing this is not only false, but other races who use rage in their mental powers exist and are actively looking for races to use as cannon fodder and slaves. They also convinced those child races that modifying a race against its will is a good thing, and they are doing it to humans. Oh and then there is the Posleen, where they took a race that was something like Ancient Greece and made them into a Horde of Alien Locusts by making them breed often and quick, and so that 9/10 would be born with a form of mental retardation except for genetic memories and gifts for things like agriculture. And when this went horribly wrong they tried to shove them off on a prison planet, and after they escaped it became even worse as they started to actively harm them to try and contain them more. Like wrecking their cultural memory so instead of actively looking for their foes, they loot and breed and plunder everyone.
In the Uplift series, the punishment for being Abusive to your client species is often extermination. Also, way back in prehistory, there was description of a group called "The Lions" who ignored the rules, ruled without any care of the potential species for millions of years (causing mass extinctions, which for the Galactic Society of the Uplift universe is tantamount to genocide), destroying lots of information about the past, and had to be put down by an alliance of Sentient Species which would have to rebuild so much lost information on Galactic Civilization and put in new safeguards.
An idea of the scale involved is that the Lions ruled the Five Galaxies for twenty million years. In retrospect this is seen as a brief, nasty interregnum.
The Shaddill from The League of Peoples Verse travelled around "uplifting" deserving species by granting them wonderful gifts of sufficiently advanced technology... gifts which would destroy the species' culture, stagnate their development, and slowly drive them into decay and extinction.
The K'chain Che'malle, the oldest race, were lizardmen who ruled the planet with an iron fist; when Che'malle survivors show up in the last couple of books, though, they turn out to be more coldly alien than evil and end up allying with the protagonists, recognizing that humans are now the dominant race on the planet.
The Jaghut were mostly a race of solitary, pacifist scholars and mages, but every so often one of them would go mad and become a Jaghut Tyrant, effectively a God Emperor to the younger races they enslaved.
The Jaghut are more of a subversion verging on Neglectful Precursors. They seem like this trope at first, but aside from the occasional Tyrant they just don't care because civilization is for wimps. And they should know, they used to have a thriving one until one of them aptly named the Lordof Hate convinced them to collectively sit down and stop being social.
The Forkrul Assail are the most clear-cut example; a race of Knight Templars obsessed with purity, they killed their own god when it didn't live up to their standards, and come back in the last couple of books to give humanity the same treatment.
The T'lan Imass are an undead Neanderthal-type race who are dedicated to destroying the Jaghut to prevent any more Tyrants from arising. They don't have much to do with modern humans (except for the Logros T'lan Imass, who got recruited by Kellanved as shock troops), but historically they have been known to wipe out whole nations if they see a need.
Before they adopted a non-interference policy, the Time Lords were pretty evil, such as kidnapping species from different planets and have them fight to the death for their amusement. Even afterwards they would act to preserve their near-monopoly on effective time travel, to the point of exterminating any species that got too close.
The Time War was not a positive influence on the Time Lords' disposition. They became so unpleasant and genocidal that the Doctor had to basically turn all of Gallifrey into a Sealed Evil in a Can.
The Silence manipulated humanity in secret for millennia and not for good ends. Supposedly they've been trying to save the universe from a future threat that involves the Doctor, but they could easily be lying. They even admit that we should kill them all on sight.
The Daemons were established as manipulating humanity (as one of innumerable "experiments" they ran on less advanced species) long before the Silence. Specifically what and when they manipulated is just part of the series' long Continuity Snarl. An Expanded Universe series of novels posits the Daemons tricked Renaissance-era humans in order to force the creation of Earth's first time-sensitives, and later pretended to be insulted by the results, arranging a massive purge to kill all of them. Turns out, they just wanted humanity to do all of the heavy lifting - first they ensure Earth has the potential for time sensitivity, and then they arrange for conditions in which only the hardiest and most experienced sensitives can survive in order to create their window of opportunity to create perfect time channelers (essentially, human TARDI Ses).
The Vorlons and Shadows from Babylon 5, who manipulate younger races to prove a point to one another. When that isn't going well enough, they start blowing up the races who don't agree with their point of view. Made worse by the fact neither of them can really remember why they are doing what they are doing anymore.
In Go-onger, an ancient counterpart of the villains known as the Horonderthals caused the dinosaurs to destroy themselves.
The Greys of The X-Files. Where to start? They manipulated some of the most powerful people on Earth into plotting against the rest of humanity (turning us against each other), abducted and performed medical experiments on us, plotted with their human allies to cover up their existence, leaving said abductees as social outcasts, planned to use the Black Oil to enslave us until we were no longer of use to them, at which point they planned to make us extinct, touched off a war with a rebel faction that was fought on Earth and resulted in tragedy for the families of their abductees, sent the Mighty Morphin' Bounty Hunter and the Supersoldiers after us, and by the way... their invasion date was set for 2012. Even then the real villain is "Black Oil", the creature(s) who took over the originally-peaceful Greys.
On a much, much lesser scale, Mayor Wilkins also counts. He created Sunnydale for the sole purpose of creating a feeding ground for demons so that he could become a pure demon himself.
Star Trek's Iconian civilization was apparently so abusive even in their own time that the other races at the time banded together to wipe them out, and are always referred to in leftover artifacts as "The Demons of Air and Darkness". Though the episode that introduced them had Picard theorise that this was a reaction to their signature technology (portals that can go seemingly anywhere) rather than the Iconians actually being evil, and the other canonical appearance of Iconian technology doesn't present any evidence to the contrary.
The gods in Greek Mythology are the poster children for Disproportionate Retribution, and have a hefty section on that page. Not to be outdone, Gaia instigated a fair number of the divine conflicts, usually as escalation from a previous conflict. She gave birth to the Giants by Uranus and Typhon by Tartarus and turned them lose on Zeus as retaliation for Zeus overthrowing and imprisoning the Titans, who themselves were pretty bad, as Cronus devoured all of his children whole in an attempt to defy a prophecy that one of his children would surpass him.
Their name does not translate to "giants". It translates to "devourers".
The C'Tan of Warhammer 40,000 definitely fit the bill, having had a massive war with the (merely neglectful) Old Ones, and given the galaxy the Necrons. 40k being whatitis, they both lost. Once galaxy-spanning races, in the game's current setting both races combined have five people left.
The Old Ones qualify too. In fact they're responsible for most of the horror of 40k. They refused to help the Necrontyr who were all dying horribly from radiation that wasn't even their fault, despite the fact that such an undertaking would be quite easy for them, prompting the war and the Necrontyr becoming Necrons. And during the war, the Old Ones created other races to fight the Necrons. Half-finished races like Eldar, who they told were their favorites and would inherit all they left behind before shoving them out as cannon fodder, and Orks, to fight and do the dying for them. They also dabbled in humanity, giving us psykers that can't quite control themselves. And all of these angry warlike races and galaxywide genocides transformed the warp from a peaceful, idyllic place to space hell. And the War in Heaven gave birth to the first Chaos God. Well done, Old Ones.
At least one story suggests they are actually thrown out of time. In one source book dealing with different blood ancestry gifts (stuff like having dragon descendants, etc.), Illithid blood powers are in the people who are the Illthids' ancestors. Thus, some humans are Abusive Precursors.
In the fan-made Aielund module series for Neverwinter Nights, the mind flayers (called Saquarin, but they use the same models and rules) are aliens who keep 'lesser races' as cattle without them knowing it, and have Githzerai agents on the planets to engineer wars so as to keep the humans (and others) technologically inferior.
Aboleths used to have a sprawling empire at the dawn of time, or maybe even in the previous universes. They have very little use for anyone not a slave or an experiment.
This trope seems to be popular for tentacled aberrations in general, as the kopru from Mystara are mentioned as having ruled a mind-controlled empire in the distant past.
In a non-tentacled aberration example, the reptilian Sarrukh of the Forgotten Realms degenerated into this. At first, they kept their sacrifices to their god to honoured Sarrukh volunteers. But then someone hit upon the idea of sacrificing all those non-reptilians, which required the use of divine aspect trickery to 'purify' the souls, which (together with the non-voluntary part) led to the sacrifices having to be in much larger quantities...
The Primordials of Exalted were often described as being destructive jerks who, when not consumed with the Games of Divinity (AKA the Magical Crack Xbox), would travel the world, messing things up for their own amusement and create hideous monstrosities and crazy concepts alongside the more normal things in the world, and tasked the gods with the job of fixing things after their destructive romps. Eventually, the highest gods got fed up, empowered mortals to defeat their overlords, took over Creation, and took the Games of Divinity for themselves. That being said, the highest gods aren't exactly doing a good job, and now the Primordials have actual reasons for trying to break things.
The Titans from Scion certainly fit the bill; the Gods rose up against them because they were horrifically abusive and locked them away.
The Scarred Lands setting (also by White Wolf, who are obviously in love with this trope) has ostensibly the same backstory. There are hints that the Titans may eventually, even inevitably return to power, that the entire 'reign of the gods' is just the cyclic stage of the particular Titan Denev, who is relatively benevolent.
The Ancients in Traveller. As they have kidnapped creatures (including humans) from Earth and sowed them on other planets that makes them a bit like The Grays, as well. The most abusive of all by far is the first Ancient, Grandfather, who uplifted the other Ancients, gave them his abusive guidelines to follow, and wiped them out when they finished what he wanted. Oh, and he's still around, watching and waiting.
The Syndics of Myriad Song, who vanished just a hundred years ago and whose former slaves are still trying to work things out.
The Reapers almost set the record for the most abusive of all. They deliberately leave Lost Technology around for future species to find to encourage specific technological developments, thus making it easier when they return to completely obliterate them and "reap" what they have sown. They do this for the purposes of reproduction, creating new Reapers from millions of harvested people. Those who aren't suitable for this are instead transformed into mindless husks, tools to be used in the next "cycle"; this was the ultimate fate of the Protheans.
The Catalyst states at the end of Mass Effect 3 that the Reaper's true purpose is to catalogue and indefinitely preserve all organic life, to protect it from the inevitable Robot War.
Mass Effect 3 also reveals that the Protheans were pretty bad as well. They ran a galaxy-wide empire, subjugating other races (if they didn't exterminate them first) and absorbing them into their culture. Their reasoning was that, with the threat of synthetic life on the horizon (represented in their cycle by the Zha'til and the Metacon War), all organics had to stand together or perish. Once the Reapers came upon them, they tried nurturing primitive species, hoping that some Protheans could sit out the destruction in stasis and emerge after the Reapers had left to lead these species against the next cycle. Their best hope (according to a guy who more or less admits to lying) were the asari (who, ironically, ended up running the galaxy themselves with wisdom, patience and diplomacy), but they also intervened upon the hanar and at least studied some of the early humans. Some of the things a party member says on Thessia suggest that there was some generosity involved with the primitive asari; Protheans took pity on them for having trouble with numbers and didn't want them to starve, so taught them mathematics and agriculture.
The LeviathanDLC puts the above precursors to shame with the Leviathans, the species that built the intelligence which built the Reapers. They shared the Reaper's Mind Control abilities, and used it to enslave the rest of the galaxy and for them to worship the leviathans as gods.
The Dnyarri in Star Control / Star Control 2 are the primary cause of the Ur-Quan's actions, both Kzer-Za and Kohr-Ah. And no, they were not nice people. For a better perceptive, they were inspired by the Thrint in Literature above... and then were made even worse.
If you want to consider Star Control 3, let's put up the Eternal Ones. Seeding the universe with sentient life so you can eat all of it? Considering that one such sentient population managed to figure out a way to make sure that no one has to die in their iteration, while the Eternal Ones went through who knows how many iterations committing universe-scale xenocide...
Not to mention ... humans, ourselves. We created an entire race of sentients, and we enslaved them for a generation until they managed to escape. That's why the Androsynth hate humans so much.
The Sarrukh "Old Ones" in Neverwinter Nights. Powerful magical humanoid reptiles forced into dormancy by a cooling climate... for now.
Elaboration in the tabletop game revealed that the Sarrukh, one of five Creator Races, had begun fairly non-abusive, but (mostly) began to slide into evil as their god fractured and fell into somnolence and an excuse was made for sacrificing non-Sarrukh (sacrificing honored volunteers are one thing. Mass sacrifices of slave races, another).
The Suul'Ka in the Sword of the Starsbackstory, corrupt, gone-mad-with power Liirian elders who enslaved the Liir, used their pawns to destroy the old Morrigi civilization and killed 90% of their male population, and created the Zuul, a genocidal race of religiously fanatic Super Soldiers. The Liir retro-plague wiped most of them out, but the sequel revealed that seven of them survived and recovered... And now they are back. And they are angry.
In the first game, Suul'ka was assumed to merely be the name the Liir gave them, their true name being unknown. "Suul'ka" actually translates literally as "winterheart" or "abomination". As it turned out, they are Liir, and they do indeed call themselves "Suul'ka". It says a lot about them that they actually refer to themselves as abominations.
Sin/Yu Yevon in Final Fantasy X is a Space Whale that originated as the most powerful summoner in Spira, who turned himself into a Weapon of Mass Destruction to defend his people and ended up so hopped up on the power that he kept the summoning going for a thousand more years. The "Precursor" part comes from the fact that his daughter organized a religion based around worshipping his name and appeasing him by throwing aeon after aeon at him, so he'd always have a new host to possess...at the cost of the summoner's life.
The Dread Lords of Galactic Civilizations II. There were two Precursor factions (the other called themselves the Arnor), one which wanted to befriend all the younger races and one which wanted to enslave them all. Guess who's who. Guess which ended up as Sealed Evil in a Can.
The Precursors who built the Sphere in Prey seeded countless planets throughout the galaxy and are directly responsible for life on Earth. And all they ask for in return is that every few thousand years, they stop by and gruesomely abduct and slaughter countless people to keep their Organic Technology running.
In The Legend of Dragoon, the creator of the world created a Tree of Life, each fruit of which is a new species of animal. Apart from the sapient species, these creatures are uniformly hostile to all life, and the final fruit, the Virage Embryo, exists for the sole purpose of destroying all life on the world.
Skies of Arcadia had an ancient and powerful civilization that decided that mankind was being too destructive. What do they do about it? Destroy those civilizations. Due to Valua's ambitions, they're thinking of doing it all again. But not before sending two agents to check it out. That cute blonde, the one who joins you after you rescue her from the Valuans? She's one of them. Unfortunately, there's the matter of the other one...
The H'riak in Alien Legacyseeded aggressive life all over the galaxy, designed to hate and destroy all non-H'riak life. The Centaurians are one such race. When they found humans, the first thing they did was attack, starting a war that resulted in most (if not all) life on Earth to be wiped out, leaving only colonies. The H'riak also seeded the two habitable planets in the Beta Caeli system with violent flora and fauna and created a race of psychiccalamari who, while not aggressive, try to kill humans because our thoughts hurt them. Also, the ship they send to Beta Caeli is also capable of causing the star to go nova as a last resort.
The plot of Ares Extinction Agenda can be summarized as follows: Some alien(s) all life in the universe. Said alien(s) have decided humanity is destructive and wasteful and should be wiped out. A robot humans built disagrees, strongly.
Done by humanity itself by accident in the Mega Man Legends series. See, humanity made an artificial slave race called the "Carbons", and to make sure they didn't go rogue, set up several failsafe systems to wipe out all the Carbons if there were any signs of acting outside usual parameters, or if Carbon population was suddenly much greater than the human population. Then the humans died off of natural causes, leaving behind the sapient carbons and several failsafe systems that thought the carbons had gone rogue, when they in fact were simply living.
For the breadth of Phantasy Star Universe and its several expansions, the Ancients are just MacGuffin providing story fodder. Then we finally get to meet a pair in Portable 2 to find that just like the current generation, they ran out of resources fighting off the SEED , and subsequently sealed themselves away in subspace. In a nice long Evil Planthey left humans to keep the system spruced up and ready for colonization via enforced Mind Fuck when they reached the ability to use subspace. About the only reason you have a chance is because one of them is a Benevolent Precursor.
For millions of years in Otherspace, the god-like Kamir and Hivers fought each other with willful disregard for the destruction they were doing to the rest of the universe, often pulling players in as proxy warriors in their machinations. Eventually, all their destruction ended up breaking the universe.
Halo's The Forerunner Saga novel trilogy reveals that the Precursors tried to exterminate the Forerunners, who struck back and wiped them out instead (or maybe the Forerunners attacked them unprovoked; it depends on which side is telling the story). It's later revealed that the Precursors subsequently became the parasitic Flood and do intend to condemn all of their creations to an existence of eternal pain and misery.
The Forerunners themselves are shown to have been pretty abusive towards both lesser species and the nearly-as-advanced humans and San 'Shyuum, ultimately culminating in the Forerunners forcibly devolving the former and stripping them of all of their technology, and quarantining the latter to a mere two planets.
The Black Moon in Galaxy Angel has become this either by corruption of its programming into being a factory of destruction or because it was built that way from the start. This makes the White Moon either its counterpart or its opposite. Even at the end of the first game it's not very clear.
In Might and Magic VIII, a non-malfunctioning Ancient construct, Escaton tries to destroy the world. As there doesn't seem to be any reason for that, this would appear to make the Ancients fit into this trope (especially as they are still out there, just rather busy at the moment)... but as it turns out, there is a reason: the Ancients, rather reasonably, put failsafes into Escaton to keep him from being subverted by the Kreegan, one of which was an inability to willingly stop destroying a world once he had started. As he only started doing it if he deemed a world unable to defeat the Kreegan, that generally worked out, but in this one case he happened to underestimate the inhabitants...
The FreeSpace series has the Shivans, though why they are so intent on destroying the Terrans and the Vasudans is a complete mystery. Theories range from them being some kind of "galactic immune system" to them being Sufficiently Advanced Aliens from another universe, but their motivations are more or less entirely unknown. The Ancient Ones were pretty bad too, either enslaving less advanced lifeforms or running rebellious/resisting races into extinction, which caused the Shivans to wipe them out entirely. It's also implied that the Ancient Ones had a hand in helping the Vasudans get off the ground, and that the Vasudans rebelled just as the Shivans began attacking, thus allowing them to continue to grow until they met the Terrans, who were probably ignored by the Ancient Ones because of the Shivans' wiping them out. To give them credit, the Ancient Ones also left behind artifacts on their home planet in the Altair System that helped the newly founded Terran-Vasudan Alliance defeat the Shivans in the first game by destroying their super-destroyer, the Lucifer, while in Subspace transit to the Solar System, to destroy Earth like it had Vasuda Prime before it.
On balance, the X-Universe's Old Ones are this. Theoretically they have good goals, such as preventing the heat death of the universe, and they consider the Portal Network they built a gift to the younger races. Unfortunately they have a tendency to think of the younger races as a single group, making them frighteningly willing to toy with them seemingly at random. Since their most direct method of manipulation is to switch gate pairs in the Portal Network, this means they do things like start interplanetary wars, separate colony ships from their home planets or lock fleets in deep space with nowhere to go, or even turn off the whole network. Then again, the network shutdown after X3: Albion Prelude came partly in response to the Xenon gaining control over a sizable portion of the galaxy, so YMMV.
Possibly justified by the fact that according to the backstory, the Old Ones have been united for over 3.2 billion years, which brings Blue and Orange Morality into play. In other words, they're so far above us that we don't understand them, and they don't understand us.
Betrayal at Krondor, just like the world from the Riftwar Saga that it is based in, features the Valheru, dragon-riding tyrants who trolled the multiverse since the dawn of time, only to be brought low by the newly-forming gods. Directly responsible for the introduction of every race in the world, as well as most races on other worlds.
The Mother from La-Mulana is hinted to be one, having created the Eight Children — that is, humankind and its seven predecessor races — for the sole purpose of engineering her return to space, from whence she came. It's stated that she is behind the destruction of a few of the previous Children for their failure to accomplish this goal, making her guilty of multiple counts of genocide (through negligence, at the very least). And there is one tablet that implies that humanity itself has an expiration date coming up in 2015.
Pre-War civilization in Fallout is pretty much a result of insane social experiments in a world where the Cold War never ended. The major example was Big Empty which in exchange for highly beneficial technology turned their clients into unwitting test subjects.
Treasure of the Rudra: At the end of every Great Cycle, a Rudra appears to commit genocide on the current residents of the planet. The Giants, Merfolk and Lizard people have already been exterminated, with just a few survivors, and humanity's time is almost up... turns out this scheme was all devised by abusive precursors, whose plan to defend against their own abusive precursors was to create a race that could defeat their rudras and, ultimately, them.
Dead Space: The Brethren Moons, the ultimate form of Necromorph existence. They deliberately seed planets with their Markers, which, once a species has grown to sufficient size, cause Necromorph outbreaks and ultimately a Convergence event, in which the entire Necromorphed population is combined into a new Moon. The reason that humanity has never found any alien life in the galaxy is because the Brethren Moons have consumed all of it, and humanity is next on their list.
The Elder Scrolls: The Ayleids who once ruled over Cyrodiil were not very nice people, to put it lightly. They kept humans as slaves, and some of their more horrific mistreatment of their slaves included forcing them all to work naked, force-feeding them hallucinogenic drugs and watching their reactions, creating sculptures out of their bones and gardens out of their entrails, and setting human children on fire and setting hungry animals on them. The humans eventually rose up against their masters,overthrew them and ruthlessly hunted down all vestiges of their civilisation, exterminating them. Humanity, fuck yeah.
And what did they do when the entrail gardens began to rot? Ground it up and threw it into the slaves' food troughs. They were also fond of skinning their slaves alive and making the skin into blankets for the human babies.
The Dwemer, who were basically Babylonian/Bronze Age Mediterranean Steam PunkFlat Earth Atheist dwarves, would also count. They were basically what happens when you put scientific advancement as the primary focus of a civilisation without ethical guide-rails to steer them along. They were ruthless, amoral and arrogant, and their activities included intentionally summoning Daedra to put their divinity to the test, using other races for experimentation and slave labour, and turning the last surviving Snow Elves into blind and feral slaves after offering them shelter and safety.
The Last Federation has Hydral. They were first into space and created lots of tech that much, much more powerful than anything else others have. They also actively prevented anyone else getting into the space, destroying anything bigger than a satellite. Their died when they were hit by Depopulation Bomb and one of the species dropped a moon on them.
The followers of the Old Ones, ancient space gods from another dimension, were the first lifeforms to colonize a primordial Earth of the Global Guardians PBEM Universe. A series of wars begin with the Old Ones on one side and U'tua the Gardener, the war-fleets of five of the Progenitor Races, and at least thirty of the Progenitors' more advanced client species, on the other. Eighteen centuries of constant warfare culminated in the banishment and imprisonment of the Old Ones to places outside the universe. The victory came at a great price, as the entire H'ch'wee and Krang species, along with every member of their various participating client species, were exterminated in the fighting. Unknown to the victors, a small number of servants of the Old Ones survived on Earth. They went into hiding deep underground.
The Titans from Erfworld built the eponymous universe with laws of physics which seem designed to make peace impossible. However, recent events indicate they may be still active.
Whatever created Sburb in Homestuck: the game in question seeds species' existence for the sole purpose of destroying it except for a limited group of children who are tested to see if they can win a difficult game. And the children don't even come from that planet, they're created by the game itself.
The trolls wanted to become this to Earth. Didn't quite work out.
In a roundabout way, Lord English is responsible for the existence of the main characters and their universes. He's currently trying his best to wipe them out along with everything else.
In Transformers Prime, Unicron is this for all life on Earth. He IS planet Earth (or at least, the center of it), and views the organisms that have come to live upon him while he slept much the same way as if you or I were to wake up covered in mosquitoes.
The "Deadly Probes Scenario", one explanation for the Fermi Paradox, is along these lines - there aren't any aliens because some ancient alien race released robots programmed to seek out and destroy intelligence. Mentioned here.