Potential for this trope is built right into the Ravenloft setting, where eliminating a domain's darklord can have three possible effects: A) another evil being is elevated to darklord status, gaining immense power; B) the domain is split among neighboring darklords, potentially kicking off invasions and so forth; or C) the domain — and everyone living there — literally disappears.
Of course the third option might be the best one for the people living there as A Fate Worse Than Death is pretty much the standard operating procedure for Ravenloft.
Urza from Magic: The Gathering pretty much lives for this trope, between the sylex blast, the soul bombs and the Tolarion Academy he probably killed as many people as Yawgmoth did in the invasion.
Urza's, and by extension, Mishra's, ultimate example of this page's topic was actually their shattering of the Powerstone that held closed the original portal to Phyrexia, allowing the entire next decade (or, in-world, 2,000 years) of storylines to happen, and ultimately tore down reality enough to cause a Continuity Rebootinside the continuity.
Jace Beleren. After getting locked in the Eye of Ugin with Chandra and (a super-sized, very draconic) Sarkhan Vol, he realizes that their spells are useless...then he realizes the "sheer flame" the scroll that led him (and her) there speaks of would work to take down Sarkhan and save both their hides. It does....it also unlocks the Eye, unleashing Ulamog, Kozilek, and Emrakul, aka the Eldrazi, destroyers of planes of existence.
Goes double for Nissa, who decided to destroy the Eye in the hope that this would make the Titans leave. It didn't.
Similarly, Glissa Sunseeker of Mirrodin block set out on a quest that ended with the overthrow of the mad golem Memnarch, whose "leveler" crushing robots killed her family. Then it turned out that despite his arbitrary and despotic habits, he was the only thing standing between Mirrodin and Phyrexiancorruption. Now, a few in-game centuries later, we have Scars of Mirrodin block, with the final set confirmed as New Phyrexia...and Glissa herself has been corrupted by the glistening Phyrexian oil.
In Scion, the titans that the titular heroes have to fight against are innately tied to nature itself, and their deaths have dramatic effects on the planet. For instance, when Odin killed the titan Ymir, it ended the ice age. All well and good, except that this is what caused the Great Flood. One can only imagine what would happen if Gaia or Kamimusuhi, titans of birth, were to be killed. Fortunately, there are cans to shove them in.
Given that the Chronicles of Darkness are to a one defined by the terms "Crapsack World" and "Paranoia Fuel", it should be of no surprise that almost every game-line presents some opportunity for this or outright incorporates it into the setting lore.
Mage: The Awakening: There is an entire realm made up of the collective dreams and concepts of humanity. Yes, you can do things like kill the entire concept of, say, Love. Accidentally. Plus, spells can misfire, the most common misfire being the spell targeting something selected by the Storyteller instead of the intended target, with the Storyteller advised to go for maximum irony.
Werewolf: The Forsaken: Spirits tend to correspond to physical places and locations. The bargains you make with those spirits can change the behavior of their corresponding objects and places in the real world.
Promethean: The Created: Your very existence is this trope, the universe hates you and rips itself apart in your presence. Simply staying in one place for too long can destroy everything.
Geist: The Sin-Eaters: Many of your powers have a radius effect of miles, and do things like change what season it is. You're a walking source point of collateral damage.
Hunter: The Vigil: The sourcebooks repeatedly iterate, sometimes subtly, sometimes bluntly, that even beyond the chance for plyers to screw it up, part of the reason the Vigil has very mixed results is that it can fall into this, due to the fact that most people are either genuinely ignorant of the subtle shades of darkness of the supernatural, too closeminded to accept that things aren't black and white, or both. That pack of savage shapechangers? They're the descendents of a long line of half-mortal half-spirits whose purpose is to keep alien totemic spirits from ripping through the fabric of reality and turning humans into puppets and food. Those crazed self-proclaimed mystics? They're actual wizards trying to restore a golden age of humanity, as well as fight off invasions from a kind of 'anti-reality'. The vampires running a trendy nightclub and secretly bleeding the human clientele? Now the civilised vampires are gonna start being a lot more brutal in their feeding habits as they struggle to find their own prey... to say nothing of the band of sociopathic-even-by-their-standards vampires who are going to take advantage of that opening to start butchering humans for the hell of it.
One fan-made gameline, Siren: The Drowning, outright exploits this: one version of the Bad Future the gameline revolves around takes place in a world where the Vigil eventually managed to go public. Of course, it turns out than in the resultant Unmasqued World, not only did they send the various monster races into full-blown war-mode, but they crippled humanity under an atmosphere of paranoia and civil war — not everyone will agree with "kill all wizards" if their sibling, parent, spouse or child is a wizard, after all. The resultant clusterfrak is essentially World War III... on steroids.
The original Hunters aren't any more likely than their Spiritual Successors to have a clue what's going on or which horrific monsters need to be destroyed and which are actually the last thing standing between the local town and a horrible, horrible death. The werewolves and other shapeshifters, for example, are fighting and dying to protect their human charges from literal incarnations of hate, torture, insanity, rape, and other pleasant things.
Then there's Werewolf: The Apocalypse itself, where it was made clear that the main reason the Garou were doing so badly against the Wyrm was because they slew first, asked questions later. Their millennia-long righteous campaign of purity resulted in the extinction of three races of Changing Breeds (and one of their own tribes), the surviving Changing Breeds severely distrusting them and each other, and a general species-wide feeling of, "Great, now what?"
Never mind the Impergium. The fact that virtually every human being who recognizes a werewolf for what he or she really is flips out, kind of putting the kibosh on any notions of just sitting down and talking things out? Yeah, that's the direct result of the millennia-long "culling" program the Garou enforced on humans in ancient times in order to keep them in check, which ultimately not just failed but is also more than just hinted to have driven humanity subtly and collectively insane — thereby of course only opening the door for the Wyrm that much wider.
And let's not forget that the War of Rage screwed the Garou further thanks to who they wiped out. Oh, you're lamenting the fact that only one in ten Kinfolk will undergo the First Change and become a full-fledged werewolf? Well, too bad you killed the wereaurochs, whose duty was literally to serve as Gaia's matchmakers and ensure breeding pairs that would be more likely to produce a full-fledged shifter. Oh, you're lamenting how Wyrm taint is everywhere? Well, too bad you killed the wereboars, who had the ability to purify tainted earth without becoming corrupt themselves.
In Warhammer 40,000, Magnus The Red used sorcery to become aware of Horus's Face–Heel Turn and desperately broke his oath never to use psychic powers again to immediately inform his father the Emperor that Horus was planning a bloody revolt against him. The Emperor, refusing to believe that his favorite son could turn against him and possibly influenced by the widespread Fantastic Racism against mutants like Magnus, instead ordered Leman Russ, who was already looking for an excuse to take out his personal grudges against Magnus, to apprehend him and bring him to Terra. The Thousand Sons legion might not have defected and brought the Chaos Marine forces to exactly 50% of the existing legions at the time had Russ not gone in guns blazing and tried to execute Magnus on the spot. Instead, Tzeench got his own personal legion of chaos marines and the most powerful psyker since the Emperor joined Chaos. Nice job, guys.
To be fair, his standing orders from the Emperor were to go to Prospero (the Thousand Sons' home planet) and arrest Magnus, preferably to be done without shooting. However, Horus appeared and told Leman Russ that his orders were to kill Magnus, which is the reason why the Space Wolves/Thousand Sons grudge started (and continues as of the 41st Millennium).
The Horus Heresy series adds an extra layer to this- the Big E didn't send Russ just for Magnus breaking his rules, but because Magnus caused the biggest Nice Job Breaking It, Hero! moment of the entire series. In trying to warn his father about Horus, Magnus psychically travels through the warp to Terra, but finds it blocked by extremely powerful wards. The rage from his apparent failure leaves an opening to Chaos to offer him enough power to break through, which he does so with haste. End result- Magnus gets his message through, but finds that not only did he destroy all the wards protecting Terra, but the psychic back-blast also fried the Golden Throne, which was supposed to be used to contain Chaos and/or access the Eldar webway. He then suffers My God, What Have I Done? and returns to Prospero to wait for Russ to arrive and kill him.
The selection of Leman Russ probably indicates the Emperor actually had at least some consent for the Space Wolves to attack. The Space Wolves at that time were the only group of loyalist Space Marines that did not find the concept of fighting other Space Marines to be completely incomprehensible. Very early in the Horus Heresy series, an entire Luna Wolf squad was killed by a single Space Marine that was infected by a demon because not a single Space Marine in their right mind could bring themselves to fire on one of their own, even to preserve their own lives, the lives of their squadmates, or even to ensure they were capable of completing their mission objectives. He could have sent several other primarchs, but he chose to send the Primarch with a grudge, a violent reputation, and a complete willingness to fight other Space Marines. The only other explanation is Plot-Induced Stupidity.
It is worth noting, that at the time, the Space Wolves were in fact trained to destroy other Space Marine legions.
Another chance to break it, hero in WH40K is the Lords of Change. They receive visions of the immediate future from their master Tzeentch, making them virtually impossible to kill. It is possible to kill them—but only if they receive false visions of the future from Tzeentch. So by killing a Lord of Change, you're furthering Tzeentch's schemes.
Though, to be honest, as Tzeentch's schemes have no actual goal besides "make things change", you can't not further those schemes. Every action you take, every thing you do, even whether or not you were born, is all just part of Tzeentch's plan of seeing how the universe will move if he does this or that.
Pretty much every major crisis in the Eisenhorn series was caused as a direct result of Eisenhorn's actions, which led to a fairly minor situation getting progressively worse and worse.
The Emperor winning the Horus Heresy is an example of the trope, according to the novels of the same name. It was prophesized that had he lost, humanity would have died out in a couple generations taking Chaos with it and freeing the rest of the galaxy from it. This is the entire reason Alpha Legion decided to join Horus. Possibly subverted, and Emperor's victory is actually the best way, as Eldrad Ultran states.
The Emperor did this on more than one occasion, according to the backlore for the game setting. In fact, the whole Horus Heresy could, in part, be considered the combined payment for many of the Jerk Ass things he did to his "sons", the Primarches.
For example, when Lorgar of the Word Bearers encountered the Emperor, he transferred his deep religious faith into deifying the Emperor, and indoctrinated his Legion of Space Marines to believe the same way. As a result, when they pacified and claimed a world, they spent an extended period of time erecting temples to the Emperor and establishing their religion as the planet's new sole form of faith before moving on to the next one. The Emperor said not a word about this for centuries, then suddenly chastised the whole Legion for both "dawdling" and for believing in him as a god in the first place. The Horus Heresy novels explain that this chastisement took the form of going to a planet the Word Bearers had claimed over a century ago, which they regarded as the jewel of their achievements for the willingness and extent they had adopted the Imperial Cult, and then razing it to the ground. Then the whole Legion, including Lorgar, were summoned to the ashes of their world and telepathicly forced to kneel and listen to the Emperor chew them out — and in front of others, for added humiliation. Lorgar goes on to fall into worshipping the Chaos Gods and is instrumental in the corruption of the rest of the soon-to-be-Traitor Legions.
Another example in this universe is Inquisitor Kryptman, who thought it would be a good idea to lure a Tyranid Hive Fleet into attacking a section of space controlled by Orks. The logic being that whoever won would be so weakened by the conflict that they would be easy to mop up by the Imperium. Since this is the 40K universe however, things didn't go as planned. The Hive Fleet and the Ork Empire did engage. However the Tyranid fleet started becoming MORE powerful due to the bio-matter it was ingesting. And Ork reinforcements started coming in from far and wide to join in the fight. And since Orks get bigger and more powerful based on the amount of combat they engage in, and combat is plentiful in this area, whoever wins will come out of this conflict STRONGER than before. Oops.
Apparently not. The Eldar have thrown their hats into the ring and have set about bio-purging the system, killing Ork and Tyranid alike. Time will tell if they're successful, though.
Update: Ghazghkull has got himself involved in the whole mess, and now the Orks are winning. This is not a good thing, as Ghazghkull is the biggest, meanest and brightest Ork warboss in the entire galaxy, and the last thing the Imperium wants him to get is a huge army of super-badass Orks on crack.
Happened to several sets of would-be world-savers in Exalted. Perhaps the best example would be the Usurpation, a noble if excessive action to protect the world from its insane custodians, the Solars. They succeeded, but 13 ghosts from the slain Solars became the Deathlords, with enough power to beat up even the strongest Sidereals with rolled-up newspapers; many of the Lunars of the time went insane, with Raksi, Ma-ha-suchi, and Leviathan being the worst affected; the Dragon-Blooded Shogunate proved to be nowhere near as good at handling the world as the Solar Deliberative despite the reduced risk of its members going insane; and then the Deathlords unleashed a plague that killed 90% of the world's population. Whether or not this is an improvement over what would have happened otherwise is hotly debated to this day, both in and out of setting.
While the Lunar Elders all being more or less insane, an even bigger issue is that the Silver Host's prolonged exile into the Wyld ended up permanently tainting their Exaltation. As a result, newly Exalted Lunars must be inducted into the Silver Pact, lest they slowly warp into gibbering insane and damn-near unkillable Chimera.
There's also the fact that in order to avoid Divine Retribution for overthrowing the Celestial Mandate, the Sidereals broke the Mask - one of twenty five constellations in the Loom of Fate, which may or may not be the only thing enforcing causality.
Even worse, in order to avoid having the Solars they just killed respawn, most likely eventually winning the conflict, they constructed the Jade Prison to trap their Exaltations... Which is how the Neverborn and the Yozis managed to get their hands on half of the Solar Exaltations and corrupt them into the Abyssals and Infernals.
Many Planescape adventures do that to the players. For example, Fires of Dis force them to recover the sword of a respected paladin. Little they know that the Big Bad is more than happy to let them obtain this weapon, now containing a powerful baatezu. The fiend possesses its owner during an important ritual, wreaking havoc in the gate-town of Fortitude, disrupting its ascension into Arcadia.
In Deadlands, both the Union and the Confederacy have elite task-forces dedicated to fighting monsters and the dark powers that make them. Both of these task-forces, the Texas Rangers of the Confederacy and Agency of the Union, have figured out that the dark powers that are behind monsters literally feed on fear. As a result, they've decided to create/uphold The Masquerade, reasoning that if the existence of monsters were admitted, people would panic and that would make even more monsters. This in and of itself is a minor example of this trope, since the sourcebooks suggest that proper education would ultimately reduce a lot of the intimidating nature of the forces of darkness; a shadowy beast killing all your cattle is scary, but a mountain lion is just dangerous. However, it's how they go about enforcing The Masquerade that really falls under this. The Texas Rangers have a bad tendency to resort to strong-arming and intimidation in order to "convince" people to shut up about the horrible monsters they've seen, which often sabotages their efforts. But the Agency really has it bad; they're known as The Men in Black Dusters, and just like their trope-sake, they favor a mixture of enigmatic stoicism, covert activity, intimidation and outright murder to cover up the existence of the supernatural... which pretty much completely undoes any good they might do by actually catching monsters.