Rolling Stone has compiled a list of their Top 25 moments from the show. To make life easier for everyone, I have put the list together so you won't have to go page by page on the RS website.
Christopher Reeves gets superpowers from stem cells (Episode 702): A cartoon Christopher Reeve cracking open a dead human fetus and sucking its spinal fluids was offensive when he was alive. Watching it now that he's dead is absolutely cringe-worthy -- and the best evidence that there's absolutely no line Trey and Matt won't cross for a laugh.
Kyle's father is turned into a dolphin (Episode 901). Season nine began with the most disgusting scene in the show's history: Mr. Garrison's sex-change operation, represented by an extreme close-up live-action shot of a bull getting castrated. Later in the episode, Kyle goes to the same doctor to get transformed into a tall, black child. His father then fulfills his lifelong dream of being a dolphin. The whole thing is so incredibly stupid that it's hysterical. Next: They wouldn't go after the quadriplegic, would they?
The shoot-out at the conclusion of Towelie (Episode 508): The character Towelie was born when Trey and Matt attempted to think up the dumbest character with the dumbest catchphrase. The result? A talking towel who always says, "Don't forget to bring a towel!" In his debut appearance, Towelie leads the boys into a confusing battle between aliens, the government and a mysterious corporation. Key line comes via Cartman: "You're the worst character ever, Towelie."
Cartman addresses Congress about stem cells (Episode 513): After getting tired of finding new ways to kill Kenny in every episode, Trey and Matt decided to kill him for good. Cartman addresses Congress in an attempt to save his friend by convincing them of the merits of stem-cell research. They finally agree after he leads them in a sing-along version of prog supergroup's Asia 1980's classic "Heat of the Moment" -- one of many songs from that era Cartman has an affinity for.
The Simpsons-already-did-it ending (Episode 607): Without a doubt, South Park and The Simpsons are the two funniest cartoon shows of all time. In this one, South Park pays homage to its predecessor by admitting that The Simpsons has covered literally every plot imaginable. In the end, all the characters morph into yellow-skinned Springfield residents.
Father Max talks to the Vatican (Episode 608): Horrified to learn he's the only priest not molesting little boys, Father Max travels to the Vatican to confront the Pope. To save Catholicism, he's forced to travel through the sewers of Rome to find the Holy Document (in a hilarious parody of Pitfall). He then confronts a race of Catholic aliens known as the Gelgamek who say they're forced to molest little boys because "the Gelgamek vagina is three feet wide and filled with razor-sharp teeth."
Cartman talks to Christian music executives (Episode 709): Realizing just how profitable Christian pop rock can be, Cartman forms a group called Faith +1 with Token and Butters. They go on to sell millions. Sample lyric: "I wanna get down on my knees and start pleasing Jesus! I wanna feel his salvation all over my face!"
Jimmy beats up his girlfriend in a 'roid rage (Episode 803): Cartman pretends to be retarded to get into the Special Olympics (before the Johnny Knoxville movie The Ringer used the same plot). Meanwhile, Jimmy takes steroids to stay competitive and beats the shit out of his girlfriend with his crutches in a 'roid rage fit.
The boys meet an insane Mel Gibson (Episode 804): One viewing of Mel Gibson's snuff film The Passion of the Christ transforms Kyle into a born-again Christian. The other boys attempt to find Mel Gibson to demand their money back, only to find out that the actor/director is insane as everybody says he is.
Mr. Jefferson turns into demon from "Thriller" video (Episode 806): Michael Jackson, er, Michael Jefferson moves to South Park and befriends all the children. The boys realize what a horrendous parent he is to his blanket and plan to break it free. Meanwhile, Mr. Jefferson's nose falls off and he proceeds to decay to the point that he looks like one of the zombies from the "Thriller" video.
Paris Hilton buys Butters (Episode 812): The girls at South Park all turn into "stupid spoiled whores" trying to emulate their new hero, Paris Hilton, who comes to town to open a new shop. When Paris sees Butters, she attempts to buy him from his parents and turn him into her new pet. In a bizarre parody of a brief moment from The Shining, Butters dresses up like a bear and unknowingly molests a passed out Hilton.
Woodland Creatures blood orgy (Episode 814): For their 7th Christmas special, Trey and Matt decide to parody John Denver's "Critter Christmas" holiday special. Magical woodland creatures convince Stan to kill a mountain lion who keeps killing the animal pregnant with their savior. Stan realizes to his horror that the creatures are actually Satan worshippers attempting to give birth to the anti-Christ when they brutally kill Rabbitty the Rabbit and proceed to have a "blood orgy" with his corpse.
Jimmy has sex with a prostitute (Episode 906): Jimmy keeps getting erections at inopportune times. Worried he'll get one at the school talent show, he hits South Park's red light district, where he encounters a disgustingly obese prostitute named Nut Gobbler. After knocking her pimp Q-Money unconscious, Jimmy picks up Nut-Gobbler and carries her into a hotel where she presumably made a man out of him.
Scientology montage (Episode 912): In what turned out to be South Park's most notorious episode, Scientologists conclude that Kyle must be a reincarnation of L. Ron Hubbard. Kyle is given a brief overview of the cult's beliefs via an abridged version of the Scientology creation myth, which features frozen aliens in volcanoes, alien warlord Xenu...the whole she-bang. Throughout, the message "This is what Scientologists actually believe" is periodically flashed on the screen.
Chef dies, gets ravaged by boars (Episode 1001): Chef had gradually become a semi-major figure in the South Park universe when Isaac Hayes (who did the Chef's voice) abruptly quit in the spring of 2006 over the infamous Scientology episode. To give him a proper send-off, Matt and Trey had the Chef (speaking in spliced-together dialogue from previous episodes) join a brainwashing cult. In the end, he falls down a pit and is brutally killed by a mountain lion and a grizzly bear.
The Family Guy is revealed to be the work of manatees (Episode 1004): Trey and Matt have never shied away from viciously mocking anything they deem lame, no matter how popular it may be. In a two-part episode too complex to get into here, Cartman finds himself at the Family Guy studios, where he learns the show is written by a giant aquarium full of manatees who mindlessly lob idea balls into holes.
Butters gets anally probed by doctors after seeing a ghost (Episode 906): Kyle and Stan get so mad at Cartman for eating the skin off their KFC chicken that they convince the whole town to pretend that he's dead. Butters take it literally and is so distraught after repeatedly seeing what he believes is a ghost that his parents take him to a psychiatrist. Butter's treatment consists of having his ass probed with a device roughly the size of his whole body.
Miss Chokesondik has sex with Mr. Mackie (Episode 507): The school is forced to start teaching Sex Ed in the 4th grade when the boys are found "milking" their dogs. The only problem is that their teacher Miss Chokesondik doesn't know the first thing about it -- at least until she has sex with the school's guidance counselor Mr. Mackie in one of the shows most disgusting scenes ever.
The Dog Whisperer tames Cartman (Episode 1007): After Cartman leaves TV's Super Nanny an asylum-bound, human-shit-eating psychopath, Mrs. Cartman calls in the Dog Whisperer to tame her son. By treating him like a disobedient mutt, the Dog Whisperer is finally able to alter his behavior.
Butters discovers his dad at a gay bath house (Episode 514): Butters was designed to be the complete opposite of Cartman in every way -- naive, sweet-natured and idiotic. When he finds his father has been visiting a gay bath house ("He went to the gym and wrestled with all kinds o' guys. He wasn't too good, though. This one black guy had him pinned down for fifteen minutes straight!"), his mother tries to drown him out of shame.
Satan throws a fit at his Super Sweet 16 party (Episode 1011): Satan's probably the most sensitive character in the South Park universe. In this episode, he decides to throw a humongous, exclusive Halloween party and, in a biting parody of MTV's My Super Sweet Sixteen, throws a complete shit fit when his life-size Ferrari cake arrives in the shape of an Acura.
The Cripple Fight between Timmy and Jimmy (Episode 503): Wheelchair-bound South Park elementary student Timmy proved to be such a popular character that in the middle of season five, Jimmy (who walks with the help of crutches and has a speech impediment) joined the cast. When Timmy gets jealous of all the attention Jimmy receives, the two get into an epic fight, which is a shot-for-shot parody of the obscure 1988 John Carpenter movie They Live.
Lemiwinks goes into Mr. Slave's ass (Episode 614): Mr. Garrison wants the school the fire him for being gay, so he shoves the class pet gerbil Lemmiwinks up his assistant Mr. Slave's ass in front of all the students. In a bizarre parody of the original Hobbit cartoon movie, Lemminks must make his way from Mr. Slave's anus to his mouth while facing a series of challenges and meeting many enchanted guides.
Cartman jerks off Ben Affleck (Episode 705): At the peak of J. Lo mania, Cartman convinces the whole town that his hand -- which he uses as a ventriloquist dummy a la Senor Wences -- is Jennifer Lopez. The real J. Lo comes to town with boyfriend Ben Affleck, who promptly falls in love with Cartman's hand. The pair goes on a date and, in a scene unimaginable on a live-action show, hooks up.
Cartman feeds Scott Tennerman's parents to him, Radiohead mock him (Episode 501): Cartman seeks revenge on an older student by killing both his parents and feeding them to him in a bowl of chile, as Radiohead (voicing themselves) look on and mock the grieving kid. Cartman had always been a sick kid, but this Jeffrey Dahmer-worthy act launched him into a different stratosphere. Trey and Matt both later claimed this was a key moment in the show's evolution.