The Real Ghostbusters had "The Collect Call of Cthulhu" episode, where the Busters managed to electrocute Cthulhu himself. In a follow up episode, the 'Busters take care of another Old One by sucking it into an artificially created black hole (probably not a bad way to take care of a powerful being).
Extreme Ghostbusters had them dealing with Fenrir, who was trying to bring about the end of the world but apparently the original crew had already captured his master Surt in an untold tale. In Ragnarok, it's Surt who actually kills the most humans.
The Justice League episode "The Terror Beyond," in which A Cthulhuesque Eldritch Abomination tries to invade earth. Given that the beatdown is delivered courtesy of the Justice League, but especially Solomon Grundy and Hawkgirl, the "Punch" part is extremely literal.
(Monsters burst out of giant pods and attack.)
Solomon Grundy: Grundy crush Pimple-man!
They had actually set up her Nth Metal mace as pretty much designed to kill Eldritch Abominations. Aquaman's trident as well, in another badass moment for the (oft parodied) King of the Seas has him beating back a legion of eldritch abominations that are trying to invade Earth.
Justice League Unlimited, "Divided We Fall": The Flash versus the fledgling god that is Braniac-Luthor. Judging by the way the fusion of Luthor and Braniac is implied, shortly after running around the entire world in seconds for a hypersonic clothesline punch four separate times, the Flash punches every single braniac molecule out of Lex Luthor's body before simply fading out of existence due to the impossible speeds involved.
The near universal Big Bad of Transformers is Unicron, who would have been impossible to defeat if it wasn't for the power of the Autobot Matrix of Leadership, which Optimus Prime had presented earlier as being prophesied as there being a Chosen One to use The Matrix to "Light our darkest hour."
Megatron was just as BAMF as Optimus, when he literally punched out Unicron (or a stone effigy of him anyway) at the penultimate season 1 episode of Transformers Prime.
Invoked - ironically, by a villain - in Hercules. Hades poses this hypothetical question to his lackeys Pain and Panic: How do you kill a god? Pain and Panic, playing along, remark that this is impossible, since gods are immortal. Hades then explains to them his plan to use his dark magic to turn the baby Hercules into a human just so he can be killed.
Azula from Avatar: The Last Airbender . At the end of Book 2, while Aang is rising into the air in the Avatar State after finally unlocking the final chakra, she shot down Aang with a bolt of lightning straight to the back, which nearly killed him (dying in the Avatar State would break the cycle of reincarnation).
Azula has nothing on Admiral Zhao, who killed the moon. Crosses over with Broke Your Arm Punching Out Cthulhu, 'cause the ocean was fucking pissed about that, and Zhao died.note Or, well, his body did, at least. The Legend of Korra Book 2 finale shows that his soul is still alive in a spirit prison, tortured by his own worst fearsWhat's worse is that Zuko could have saved him, but Zhao refused to grab his hand.
In Book 2 Episode 10, The Library, the gang succeeds in escaping from the Knowledge Spirit not with bending...but with Sokka dropping down with a death from above style blow to the head with a book. It practically knocks the spirit out cold.
In the finale, Vilgax successfully kills Diagon by baiting him into attacking a device that absorbs energy. Since Diagon is an Energy Being, that allow Vilgax to absorb him, turning in a Physical God in the process
Ironically, Ben then defeats Vilgax in his Diagon-powered form thanks to George's sword.
Dante's Inferno: An Animated Epic - At first it seems like Dante broke his arm punching Cthulhu, since he ends up only defeating Lucifer's shadow form which accidentally releases his true monstrous form from his frozen prison in the ninth circle of hell. However, being a fallen angel of god and ruler of hell, Lucifer proves a rather unimpressive villain as the fight between him and Dante was not completely one-sided. But Dante doesn't truly defeat him until (with a little help from God) he reseals Lucifer back into his prison.
When he gets loose, Finn ultimately beats him once by using the Power of Love to tear the top part of his skull off with a sweater. When he returns possessing Princess Bubblegum and goes One-Winged Angel, Finn has an Enemy Mine with Ice King and they manage to freeze him solid to beat him.
Princess Celestia herself is on the receiving end of this in "A Canterlot Wedding, Part 2", courtesy of QueenChrysalis. Everyone, Chrysalis included, was surprised by that outcome.
In the Gargoyles two-parter "The Gathering", Oberon, lord of the Third Race, arrives to claim Xanatos's child, changing into a half mile tall version of himself and putting the whole city to sleep while attacking the building. Xanatos and the gargoyles fight back with all manner of high technology and get him on the ropes (though Xanatos Sr.'s harpoon gun and Fox's magi-blast seem to do the most damage). Ultimately, though, they end up negotiating with him.
Season3 of Star Wars: The Clone Wars had Anakin simultaneously defeat the Daughter and the Son, the embodiments of the Light and Dark Sides of the Force respectively.
In Fantastic Four, Galactus comes calling again and a number of Marvel's heroes come in for the save. The one who drops Galactus? Ghost Rider, who nails him with his Penance Stare, making Galactus scream out in agony over the countless lives he's snuffed and drop to the ground.
One Halloween episode of Celebrity Deathmatch had one of the fights be between The Undertaker and a demon named Captain Doody. The Undertaker wins, though he only manages to drive Doody out of his human vessel, not kill him.