To be fair, Did you just RAPE Cthulhu is also an accomplishment. In the last Episode the UnravellerofMysteries, a literal God of Evil undressed and penetrated Ami. Ami wasn't really enthusiastic about it and after it was over the Unraveller told Ami to call her up again. But Ami doesn't think so, because really, she didn't feel a thing while it lasted and was only sore afterwards.
A mod over at Toho Kingdom writes yearly holiday themed fanfics with members of the site as character. Last Christmas fic featured Cthulhu as the main villain. After the military fails epically to kill him, they get a pair of mecha from Santa Claus and manage to kill him.
In Dumbledores Army and the Year of Darkness, Ernie Macmillan has the stones to punch out a Dementor. Yeah, he goes down... but he tried. And he gave his secret wife, Susan Bones Macmillan time to whip out her wand and summon her Patronus.
During his first appearence in the Tamers Forever Series Chaosgallantmon absolutely DESTROYS both Azulongmon and Zuqhaiomon in about ten seconds flat.
In Manchester Lost, Crowley punched Lucifer - In the FACE!!! There's also the part where War yells, "Mommy, you're an idiot!" followed by decapitation.
The Spore wiki fiction universe has a rather epic one involving the hero fighting and actually defeating Satan(A.K.A. Kamik'Shi) and then sealing him in the sword that stabbed him.
The Mane Six's previous defeats of Nightmare Moon and Discord, of course, but they add two to the count with the defeat of Nightmare Whisper and Applejack teaming up with five alternate versions of herself to defeat Nightmare Mirror.
Pinkie and Minty managed to defeat Princess Luna with a musical number during the Cosmic Retcon of G3. Even though Strife had weakened her, that's still a great accomplishment.
The Paradise Estate Ponies, even taking into account they had three Alicorns supporting them (all three were considerably weaker than him), managed to defeat Discord in a straight up fight with the Rainbow Of Light. Unfortunately, Galaxia decided to shatter him, allowing him to Body Surf into a new body.
Dark World!Spike manages to get the upperhand on Rancor, the Draconequus of Violence, Passions, and Anger, and force her into retreat temporarily. She is a young Draconequus, but still.
The Dark World Mane Six managing to defeat Odyne!Cruelty, first destroying her body (unfortunately killing the possessed Sparkler in the process), then by blasting her soul with the Elements, banishing her from mortal reality.
A flashback episode gives the G1 Cast another example by defeating Lilith, the First Witch and a being composed of pure evil magic that could have destroyed the entire world, by Magic Star sealing her magic in the newly forged Alicorn Amulet followed by Megan blasting her with the Rainbow of Light to finish her off.
The Rumors Arc has the Outer Concepts appear as villains, so it's natural this trope would show up. The CMC and the Blank Wolf manage to defeat Moon Howler (an avatar of Nyarlathotrot made to be an Evil Knockoff of the Blank Wolf), Flash Sentry, Sunny Days (who was turned into her own entity by the spell rather than an avatar of Celestia), and Golden Tiara managed to expose and kill Beldam's physical form, and the CMC and Pip's ship the Moon Pearl manage to kill Shub Neighurath's avatar combined with the shockwave of Scootaloo freeing Rainbow Dash.
In the end, Applejack takes on Nyarlathotrotto let the CMC continue on. While she manages to damage him several times, this trope really kicks in when Dark World!Nightmare Mirror sacrifices herself to protect her, then gives AJ her power to transform her into an Alicorn, Veritas. Applejack ends up playing this trope literally by defeating him using all of her Alicorn power to literally buck his soul out of the universe.
From the same creator as the above, My Little Pony G3 vs Hatred ends in with the G3 Ponies using the combined love and tolerance of all four My Little Pony series to defeat an Eldritch Abomination born from (or acting upon) the combined intolerance and hatred of G3 the fandom has (Alexwarlorn often takes meta and fandom tropes and makes a Cosmic Horror Story out of them).
The Stallions Of Harmony Verse: Early in the story, Shining Armor declares that he would punch Princess Celestia if she would ever go evil, earning him the "Princess Puncher" nickname. Eventually he does that to Tyrant Celestia in a nightmare. Later it is Prince Blueblood instead who punches Nightmare Moon. And that was after all other stallions, stronger, more combat experienced, couldn't so much as touch her. Needless to say, it wasn't very effective and only managed to piss her off even more than she was.
In the one-year anniversary chapter of You Got HaruhiRolled!, the author wreaks havoc by summoning a giant, animate cheesecake which goes about destroying everything it comes across. The author spends so much time gloating that he is unstoppable that he doesn't notice the main characters travel through his portal to another of his fanfictions. The fic they travel to is The Obesity of Haruhi Suzumiya, an Alternate Universe fic in which every character is morbidly obese. They take this fic's version of Haruhi with them, and she devours the cake in a matter of seconds. Not to be outdone with that, Kyon defeats the author by informing him of the existence of a truly NSFWDoujinshi. note Which actually exists, but I would advise against looking for it. The author's disgust makes him sink into a literal Plot Hole, and Haruhi sits on him.
Austraeoh: a flashback in the second installment, Eljunbyro, has Rainbow Dash, enraged by her friends' death, single-handedly channels the Elements' power to turn Discord to stone. She then proceeds to smash the statue to pieces.
In Odrsjot, Rainbow at one point manages to knock out the Dragon matriarch Nevlamas - with some help from the Element of Loyalty.
Harmony Theory: Rainbow, Astrid and Star Fall actually manage to chase off Nightmare Umbra. However, Umbra is still regaining her strength.
Death Note Equestria: When Applejack is exposed as the Third Kira, she hits Princess Luna hard enough to send her stumbling back.
RWBY Reckoning: Darrel, with no weapons, and in a restricting school uniform, engages in a brawl with a BoarbatuskGrimm. He wins by means of an Aura-charged punch that sends the Grimm flying through several walls.
The Conversion Bureau: Cold War: When Princess Xenole... I mean, Celestia repeated threatens a UN conference full of world leaders, and kidnaps and tries to justify the forced conversion of over 2,000 Chinese civilians, Ronald Reagan finally has enough of her shit and punches her right in the face.
Almost literal example in a fanmade Death Battle on devaint between Godzilla and Cthulhu. It ends with Godzilla kicking Cthulhu so hard Cthulhu splits in half, and rips on of the halves up until there's barely anything left of it but mush and incinerates the other with his Breath Weapon. The maker of the fight points out that Cthulhu being described as reforming made his apparently immortality seem more like a high grade Healing Factor that could be overcome if he's damaged enough, especially since Godzilla in a bad mood is often very thorough when he makes sure his enemies are dead.
Cream and Cheese (of all people) manage to defeat Astorath the Prince of Darkness via Eye Scream, stunning him enough so Knuckles can uppercut him right off the Typhoon.
In the climax, Demon admiral Firmus D'Arnazhee is so enraged when he discovers the conspiracy behind the Metarex war that he takes out his sidearm and shoots the devil in the back. It doesn't end well.
Cosmo (yeah, that one), empowered by Venus's demonic scythe, takes on both Astorath and Beelzebub, the two most powerful demon leaders. She wins until she loses control and Astorath overpowers her.
Sonic manages to seriously hurt Maledict himself by impaling him with his own sword and rupturing his armored shell.
Samwise Gamgee's canon Cthulhu-punching is lampshaded in the Lord of the Rings fanfic Left. Frodo is astonished when Sam tells him about his battle with Shelob, and he's even more astonished that Sam does not seem to acknowledge how spectacular it was.
Queen of All Oni: Jade killing Kaito and Ikazuki probably counts as this. Meanwhile, her and Blankman managing to temporarily hurt Nameless during the fight in the Vault of Endless Night definitely does.
Speaking of Blankman, a flashback reveals how he singlehandedly managed to kill the entity that the cult he was raised in worshipped. For bonus point, it was implied to be the freakin' Slender Man.
During the final hours of Light and Dark The Adventures of Dark Yagami, the entire universe is destroyed by Blud, who does it by just spitting. Upon escaping the resulting black hole by entering the Shinigami Realm, Dark has a hand to hand battle with Blud, and manages to win out.
Vaati was only supposed to keep Discord distracted while the Mane Six retrieved the Elements of Harmony. No one was expecting Vaati to actually curbstomp him.
Fluttershy's Stare is strong enough to break Ganondorf's control of Volvagia, leaving her free to leave and hand over the Element of Kindness without a fight.
The Battle of Ponyville has several examples — Derpy, the Doctor, and Maulgrim manage to kill Phantom Ganon, Nigellas and Vinyl Scratch take down Mothula, and Discord and the CMC team up to destroy Majora's Avatar (with the latter three earning their Cutie Marks from it).
Vinyl gets another one during the Battle of the Crystal Empire, when she kills Argorok in order to defend a wounded Octavia.
During the Final Battle of the second season, the Mane Six resurrect and then promptly destroy Demise for good, allowing Ganondorf to die for good and breaking all of Demise's curses.
In Wonderful, Taylor (a. k. a. "Wonder Red") and other refugees fought Leviathan when it ripped open the shelter where they were hiding. Wonder Red's first attack was actually a giant punch.
Children of an Elder God: Shinji, Asuka, Rei (and later Touji and Hikari) spend the whole time fighting and slaying cosmic horrors of the Cthulhu Mythos. And since they steal their powers upon killing them, they can fight them even without their war mechas.
In chapter 11 of The Second Try Asuka punched Kaworu in the gut. Later on, she gets the drop on him after he takes control of EVA-02 and uses it to tear apart NERV to get to Lilth. Unbeknownst to him, she hid herself inside Unit-02, and overrides his control right as Shinji makes his appearance in EVA-01. Kaworu is so surprised at this that he actually drops his usual smile for a look of pure shock.