Angel Moxie: Miya gets an epic one at one point when she summons a demonic army to challenge the girls and hammer home the importance of training... nearly getting the power trio killed in the process. Leads to a major What the Hell, Hero? with ramifications lasting the rest of the strip.
During the 1999 arc of Asperchu, Jivin stops past Bionic from committing suicide over Ian's rejecting of him. Considering the things Bionic would do in the present, it might have been better for everyone to let him die.
At one point in Commander Kitty, the heroes have somehow accomplished their daring mission: saving 45% of the galaxy along with several other members of royalty, and have even given the villain a Heel–Face Turn. All they would have to do is play nice for a few minutes, and then leave, and they would still be handsomely rewarded. But then they decide they want all the credit, and Nin Wah decides to mock the now-good Zenith because she's a robot, shutting her down, leaving the station crippled, putting them in a worse place than they were to begin with.
During the "Sin City" (no, not that one) arc of Dominic Deegan, Dominic reveals to The Infernomancer that the demon lord he was supposedly bound to serve didn't have control over him, meaning he didn't have to follow any orders. The Infernomancer's response? "Now I get to kill you the way I've always wanted to — slowly!"
Not to mention the "War In Hell" arc, where Dominic helps out Karnak the whole time only to realize he probably shouldn't have been helping Karnak this whole time.
In his defense, Karnak's death would have also killed Szark Sturtz, since he and Karnak will linked by a wound Karnak had inflicted on Szark when the latter was a child. You really can't blame Dominic for trying to keep his best friend alive. Plus, as pointed out by Dejah, there was really no way for the war to end positively for humanity.
And then there's Klo Tark, who started a prison break to (rather circuitously) save Dominic's life.
8-Bit Theater has a nice scene where Muffin Dragoon's pet parrot (dragon) reveals to the light warriors that Bahamut, who they had previously awakened, would only awaken when the world is about to be destroyed. Only Red Mage seems to care, though in retrospect any acts of "good" the Light Warriors do usually makes everything worse for someone else.
In El Goonish Shive, Abraham and his great idea to make the Dewitchery Diamond. What he needed was to remove or suppress the lycanthropy of one guy. What he did is create a Booby Trap for unaware shapeshifters and users of cosmetic magic, with side effects that in turn suffer several other side effects in such a way that whatever problem caused its activation spreads. And it's nigh indestructible, so all this fun never ends. Worse, good ole' Abe thinks it might be intelligent! His story is apparently now used as an object lesson in what not to do with magic.
Abraham: You've heard of me? Raven: Every properly trained mage has heard of Abraham, the idiot apprentice who recklessly enchanted a massive diamond instead of selling it to to pay someone more skilled to save his noble friend.
A recent Exterminatus Now comic had Yuri smash a panel that she thought was the power source for the daemon portal. Turns out, it may have been the control panel, given that its destruction released the daemons.
Follower: Dr. Wolzarski's suggestion leads to General Richart getting his first successful combat test, which is exactly what Col. Harren and Dr. Calway were trying to prevent.
The FreakAngels had wanted to cause a huge but non-threatening destructive gesture as a means of putting the army off the notion of continuing to chase them (or at least distracting them for a while. Instead, their severe underestimation of just how powerful they are caused them to inadvertently cause destructive shockwaves which ended civilisation.
Much earlier, a totally-ignorant-of-her-true-bloodlines Agatha Clay blows her stack when groped by a minor researcher on Castle Wulfenbach and tells the man to go do whatever it was he should be doing. Bad News: the guy is a thoroughly conditioned sleeper agent of the mysterious long-missing entity called The Other, who happens to be the mother of the teenaged girl that was screaming in his face, and her voice is close enough to her mother's to act as a Compelling Voice to said sleeper agent.. Worse News: a creation of The Other known as a Hive Engine was recently brought aboard, and activating it to unleash the monsters within is exactly what The Other's servants should be doing.
Congrats, Big Ears! Your Critical Failure at healing Complains' fractured arm has lead directly to Chief dying a slow, agonizing death.
In the first chapter of Gunnerkrigg Court, Antimony helps a lost Shadow-Man return to his forest home, by assembling a Robot to escort him there (since the rules prohibited Annie from going herself). She also tells Robot that he only has to return to the Court afterwards if he wants to, so he decides to go exploring the woods. Several chapters later, Robot returns, possessed by another, violent and malicious shadow-creature, and the process of stopping the shadow results in Robot getting impaled on a BFS and deactivated. A few chapters later, Annie finds out that the people of the forest have not been on good terms with the Court for the past decade, and that they hate technology on principle. (Eventually things do turn out okay for Robot and the diplomatic incident is resolved when the Forest tries to use it as a frame-up job. The bigger problem may have been letting Robot meet her friend Kat.)
Jade sends her friend John a birthday present. Using her precognitive abilities, she sends John a weapon to fight Jack Noir. Unfortunately, the Noir intercepts the gift and ends up using it to defeat the black queen and take her power. Jack then uses this power to singlehandedly obliterate both the black AND white armies and destroy the entire planet of Prospit, which ends up also killing Jade's dream self.
In Act 5, we finally find out why the Trolls think the kids fucked up the game so badly. It's actually their own fault, as Vriska made John fall asleep, forcing Bec to prototype Jade's kernelsprite with himself, and granting Jack Noir near-omnipotence.
Then there's Karkat's big screw-up, which more or less caused everything that ever went wrong. He was in such a hurry to beat the game that he decided that the final frog needed to fix Bilious Slick's genetic sequence was unnecessary. Turns out that code was the only thing preventing the frog from getting a massive tumor, meaning he essentially gave the kids' universe cancer.
Played with during The Green Sun incident While Rose and Dave and the rest were trying to destroy it, they end up creating it with their actions. Aside from all the complexities of predestination and causality, the Green Sun isn't a bad thing, it's a neutral power. While it powers Doc Scratch and aids in the creation of Lord English, it also powers Bec, and he's the one who saves Jade and makes sure she gets in the game.
During Homosuck, Dirk tries to destroy Caliborn's soul, but instead traps it inside Lil' Cal. This wins the fight, but because of this Cal is able to give birth to Lord English, who is a universe-destroying demon and the Big Bad of the series.
Unifying the northern races to fight against Legara, but his search for more allies, led to them being too late to join the major battle against their common enemy which led to the death of a supporting character and the capture of another.
And now killing Aellon, ruining the chance of the people of Kethenecia to achieve a lasting peace with Legara, action which finally causes Benny to leave him and the party to split and forcing them to retake the adventure after a Time Skip.
In Narbonic, Artie the super-intelligent gerbil decides to literally make friends by dosing several other gerbils with intelligence serum. One of the gerbils escapes and creates a group of Objectivist hamsters. Later on, Artie meets the hamsters and gives them a million dollars which they use for their plan for World Domination. Even later, Artie breaks up Helen and Dave's relationship as he believes that Helen is taking advantage of Dave. The break-up precipitates Dave's Start of Darkness. During the efforts to simultaneously thwart the hamsters and Dave, Artie brings up his status as Token Good Teammate, and Helen calls him out on it.
After defeating Xykon and scattering his forces, Spoony Bard Elan activates a self-destruct rune that blows up the entire dungeon, because he wanted his dramatic Outrun the Fireball scene. Turns out that the self-destruct took out the magical Gate that was sealing away a world-destroying abomination, so the loss of the Gate brings the world one step closer to destruction. The only consolation of this massive act of stupidity was the Gate couldn't be recaptured by the Big Bad later on (and the Order wouldn't have known that he might try). They ultimately decide that in hindsight, this was the necessary thing to do, even if they didn't know it at the time.
In his quest to destroy Xykon, Roy, who does not understand phylacteries, inadvertently sends Xykon retreating to his tower to recover, a tower which has fallen into the hands of a hobgoblin army easily capable of conquering walled cities, making Xykon far more dangerous than he was at the start of the story.
Later on, Miko Miyazakidestroys the Azure City Gate unnecessarily. Worse yet, she chooses precisely the wrong moment to do so. If she had been stalled for even a few more rounds, XykonandRedcloak would be dead, which among other things would have denied the goblin army its powerful and competent leadership.
Later yet, Celia manages to reach a settlement with the local Thieves' Guild. While this fixes a lot of immediate problems, one outcome was that Haley(who deserted the Guild in the past) must give 50% of her loot to the Guild to maintain the fiction that she never really left. Since she needed all of it for her "get her father out of jail" plan, she is... upset, to say the least.
To make things worse, Haley doesn't even have most of her past few years' worth of loot any more, having lost most of a dragon's hoard in a fire. Just to break even, she'd have to steal twice that much all over again and give it all to the Guild — half belonging to the Guild outright, and the rest paying off her debt to them. Haley's solution? Desert the guild all over again, killing Crystal while she's at it, when the Order gets together again. the bonus strips in the print version reveals that her main justification was actually that the guild never intended to honor their agreement and was trying to kill her under the nose of her allies as "an accident" in ever more obvious attempts that fooled nobody, those were cut from the web version for pacing purposes and for the sake of having some bonus content for the paying customers, the author did not realize his mistake until much later and lamented the accidental change in plot and tone that was created by omitting those strips from the free web version
Girard, one of the creators of the Gates, was paranoid that his former associate and fellow Gate-maker Soon would break their vow and try to interfere with the Gates. So he gave Soon, and nearly everyone else, the wrong coordinates, booby-trapped the decoy area, and gave the real location to the one person he trusted, Serini. Thing is, his associate never broke his word, being a paladin. When the decoy area is approached years later by the Order of the Stick to try and defend it from Xykon, they're almost killed by Girard's paranoia and have no idea where the real location is. And guess who has his bony hands on Serini's diary?
In Start of Darkness...
Lirian: Even if you locate them, my friends will stop you from conquering the other four Gates.
Vaarsuvius, while drunk on the power of three epic evil spellcasters, defeats a black dragon that was menacing his/her family. He/she casts the genocidal spell Familicide on the dragon, exterminating the dragon's entire bloodline. Later it's revealed that Girard Draketooth, the epic-level illusionist that is charged with protecting one of the all-important Gates, was the grandson of a relative of said dragon. Thus he and his family were wiped out by the spell, leaving the Gate defenseless. He/she then went on to attack Xykon, resulting in Xykon and Redcloak finally getting motivated to move out and attempt to capture another Gate, since they'd gotten complacent after conquering Azure City.
In Penny and Aggie, when Stan confronts the sociopathic Cyndi about her attempt to deceive his best friend Jack, and other classmates, into thinking she wanted to sleep with them, he taunts her for not thinking big enough, so as to imply she's lost her touch and shake her confidence. Instead, she says "You're right. You're so right," and giggles ominously. Stan himself admits in the next strip that he made things worse.
Robyn of The Phoenix Requiem keeps doing things that look like a good idea but turn out to have horrible consequences later. Fighting the shades with water contaminates the river they drink from, which spreads it faster. Convincing Jonas to go to Hyde makes the plague follow him there, wiping out the whole town. Having him dispel the shades almost kills Jonas and strengthens the Spirits, who were shortly ago revealed as the bad guys. And having people shelter in the church only worked because Jonas was there to dispel the shades. When he's not, it's just an easy way for them to infect many people at once.
Lightning is indirectly directly responsible for the destruction of the Humankind Security Committee headquarters by the villains and the subsequent deterioration of the system that kept supublics in check. Having fired Gale from his sidekick position, Gale became a villain and then later tricked Lightning into leaving the Committee completely exposed.
In season two Nightmare ends up solving the power problem of the "Alex Project" after inadvertently imbuing her powers into all the Forcebites due to her annihilation of the Alex clone army. Thus, the complete Alex was born.
When Torg exorcises the demon K'Z'K out of Gwynn, he sets K'Z'K free upon the world. Subverted in that this was actually intentional: they needed the Demon out of Gwynn so that they could use their plan on it directly and not harm her. However...
Done again almost immediately afterwards, when Riff's attempt to freeze the demon in time actually sends it back in time, creating all sorts of havoc during the middle ages.
Spacetrawler features a group of protagonists on a quest to liberate the Eebs, a Slave Race of super-intelligent aliens who've been "brain-clamped" into having no will so they can be exploited for technology. They successfully rescue some, only to discover that un-clamped Eebs are actually a race of natural sociopaths with incredibly powerful telekinesis. And a dozen of them working together can firestorm an entire planet from orbit in seconds. Oh, and they're also kind of pissed about being enslaved. The rescue mission ends up with a body count in the billions.
Stand Still, Stay Silent: Mikkel shoves a box of books down the throat of a troll to keep it from attacking Sigrun. Problem: getting these books was the very reason they were in that Abandoned Hospital in the first place, so they have to run after it and kill it to get the books back anyway. They eventually manage it, but disturb a bunch of dangerous ghosts in the process.
The crew (mainly Quine, though Vanderbeam initiated it) have done a Nice Job Ruining The Quel's Utopia.
The Anthelerix. Both cases were such colossal screwups that Vanderbeam has since repeatedly suggested that Quine would do a better job of doing his job if he were to just sit quietly on the Paradigm someplace where no one has to look at him.
That comment is more due to Vanderbeam's irrational hatred of Quine. In the Anthelerix's case, the responsibility arguably rests with Admiral Huff. You'd think that the Paradigm being teleported back to Earth was a sign that maybe the Anthelerix didn't want anyone disturbing them for the time being, but noooo...
In Tales of the Questor Quentyn is sent on a quest to slay a dragon. He actually succeeds, but only after that success does he learn two critical facts:
There were two dragons, not one.
The one true Berserk Button for dragons is finding the body of a dead dragon.
The direct consequence of this is that the second dragon runs amok and lays waste to the Duchy Quentyn was trying to save. There are also hints that more long-term consequences await Quentyn in the form of a Corrupt Church whose attention was grabbed by this incident.