Einsteinian Roulette ends with the Lurker and the Eater of Stars converging on humanity, and the very laws of physics changing to make life impossible. In the words of Steve, "WE HAVE LOST."
The 2006 flash animation, World 2-4: Retaliation, has Bowser waging war on the Mushroom Kingdom as revenge for Mario killing him in World 1-4: Mario Vs. Bowser. He bursts through every door and effortlessly swats away any Toad that impeded his progress. With Princess Peach backed into a corner, Luigi charges straight at Bowser, only to eventually be held down by two Koopa Troopas he incapacitated during the fray. He's then forced to watch as Bowser kills the princess with one fierce hit and retreats. The movie ends with Mario and Luigi burying the princess while her remaining subjects look on.
The Slender Man ends up killing, enslaving, or inducing madness in almost every person he encounters. It's in his nature. Slender bloggers are Doomed by Canon. The best you can hope for is delaying him long enough to run and spending the rest of your days looking over your shoulder, waiting for him to catch up. The tradition was probably started by Just Another Fool, in which the Slender Man killed every single character involved in the blog.
It is debatable on how infallible this is. Marble Hornets continues to be updated even after the protagonists are caught be Slendy, and somehow escape. Everyman Hybrid looks like it's headed this way, considering how much of the cast has been killed off.
It all balances out in the end, though. Riz's family moves away and disowns him, and though he manages to make a decent living off of his fame, one of the escapees eventually tracks him down and kills him in his own home.
In SOTF-TV, Karen Ruiz goes home safe and sound after killing 10 people.
Due to the dozens of SCP that spell absolutely certain doom for the Foundation, civilization, the human race, Earth, the galaxy, or reality itself, this is eventually going to happen despite the Foundation's best efforts to avert it.
On a more microcosmic level, a handful of SCPs have evaded any attempt the Foundation has made to contain them:
SCP-1048 has successfully tricked the Foundation into giving it free run of the facility by pretending to be harmless, and since the reveal of its true nature, has evaded every attempt made by the Foundation to capture it.
The Foundation has also given up on safely containing or killing SCP-2317. It's expected that it will end the world in around 30 years.
The Nostalgia Critic's 2008 Halloween Special had Teddy Ruxpin come back from being beheaded, put a gun in the Critic's mouth, force him to do a positive review, and kill him when he screams for help.
In Yu-Gi-Oh! The Abridged Series Episode 49, Crumbs surprisingly defeats Tea and takes control of her body, despite it being a sharp deviation from the original source material, which the series rarely defies.
In the second season finale, "Melvin'd", while the heroes are busy partying, Melvin defeats Marik and Florence (who can only sit back and sing "Stand By Me") and cancels the series.
The Undersiders in Worm manage, through a combination of coincidence and competence, to take over the city over the course of the first nineteen character arcs.
Heavily mitigated by the fact that the Undersiders are the protagonists, at most barely as evil as the government, more interested in the safety of the citizenry than the local government leaders, by far superior to all of the villains they dispose of, and at the hands of the Undersiders, Brockton Bay's quality of life drastically improves after several catastrophic events. And the protagonist joins the government, greatly improving it's efficiency as a crime-fighting organisation, and the Undersiders go on to being instrumental in saving the world.
Though he is consigned to a Fate Worse Than Death, Jack Slash still manages to convince Scion to destroy humanity. Jack is removed from the picture for good, but he got exactly what he wanted, and literally billions of people die before Scion is stopped.
Tom Collins, the leader of SWAG, got his wish for Demo Reel productions to be destroyed and Donnie to die miserable and alone.
While more of a You Can't Thwart Stage One, RWBY Volume 3 ends with a major victory for the villains. Cinder Fall (who works for Salem) kills Pyrrha by shooting through the heart (and also literally through her heel), Beacon is in ruins and crawling with Grimm, the city of Vale is overrun with Grimm, and nobody is trusting of each other, and Team RWBY is completely separated, with Ruby joining Jaunne, Ren and Nora, Weiss being taken back to her home by her father, Blake on the run, and Yang is stuck in bed, having lost an arm, still in a huge Heroic B.S.O.D., possibly to the point of hitting the Despair Event Horizon, due to also losing her fighting will, too. Although Salem says that her grand scheme is beginning, the villains have pulled off their plans with great success and have come out on top.
Tellygunge's very NSFW original story, The Crow's Nest, ends with Lucinda Crow, along with her partner, Rachel, performing a massive Humiliation Conga upon Amanda and Helvetica that ends with the latter 2 getting a Traumatic Haircut, then put into an Unwinnable Joke Game where in theory the loser won't be humiliated on-stage. That humiliation is attempting to get the other to orgasm in a verymessy state, but both go out on stage anyway (where the entrance is a giant vagina), where they climax while glue and black feathers cover the victims. Only for the story to end on a non-lethal Bolivian Army Ending for Lucinda where Rachel gets her drunk and plans to humiliate her herself.
Death Battle has three instances of villains triumphing over heroes. "Godzilla vs. Gamera" has Godzilla destroy Gamera during an attack on a city and "Ryu vs. Scorpion" has Scorpion incinerating Ryu in the netherworld (though this is played with as both Godzilla and Scorpion are more of particularly violent Anti-Heros than true villains). "Hulk vs. Doomsday" ends with a straight version, with Doomsday delivering a savage No-Holds-Barred Beatdown to the Hulk before ripping his head off, leaving Doomsday to continue his rampage with no one to stop him.
It's also played straight when you have Evil Versus Evil episodes; "Shao Kahn vs. M. Bison" ends with Kahn killing M. Bison by ripping him in half and then absorbing his soul, and "Joker vs. Sweet Tooth" ends with the Joker, while badly injured from being impaled on a pipe, tricks Needles Kane (the driver of Sweet Tooth) into getting out of his vehicle to try to kill the Joker close and personal, only for the Joker to spray gaseous Joker Venom into Needles' face, causing him to die laughing.
This can even happen in episodes where both combatants are heroic, such as Gaara vs Toph, which has Toph intruding upon sacred ground and attacking Gaara when he asks her to leave, culminating in her crushing him to death in his own sand armour, and Yang vs Tifa, which has Yang attacking a bouncer, damaging the property, scaring away the customers and attacking the bartender for trying to have her removed from the premises, culminating in her snapping Tifa's neck. They may be heroes in their own series, but in these episodes, they are most definitely anything but heroic.
The Flipbook Studio short film "Bogeyman" ends with the Bogeyman succeeded stealing The Child's soul
Pen Pal is about Dathan, a man whose early life was riddled with tragedies thanks to the relentless pursuit of an insane pedophile who happened to find a kindergarten project. For over a decade, he pursues Dathan from afar, takes up residence in the crawl space under his old house, and even kills people who he thinks are too close to him. These include Dathan's neighbor, his best friend's sister and potential girlfriend, his cat, and eventually his best friend Josh. So how does this psycho ultimately meet his end? After kidnapping Josh and forcing him to pretend to be Dathan, doing lord knows what to him for years, he traps the two of them in a box that he pays Josh's father to unwittingly bury. After it's excavated, the stalker's body is found with a peaceful smile on his face. He got exactly what he wanted in the end and died without ever paying for his crimes.