Shrek's appearence is based on that of pro-wrestler Maurice Tillet, a man born with a rare disease called acromegaly.
Beavis & Butthead
Mike Judge based the look of Beavis & Butthead on two professors he had at UCSD.
Joker's signature look is derived from the 1928 film The Man Who Laughs. Of course, that movie is super creepy.
Quasimodo gets his signature appearance from an actual historical figure, a sculptor working in Notre Dame in the 1800's.
Winnie The Pooh
Winnie the Pooh is based on Winnipeg the bear, a small black bear who lived in the London Zoo.
The creators of Sonic based the appearence of Eggman on Theodore Roosevelt… and an egg.
The Cohen Brothers' inspiration for Jeffery 'The Dude' Lebowski was producer and politcal activist Jeff Dowd. Apparently Dowd also enjoyed white russians.
Christian Bale said he based his performance of Patrick Bateman in the film 'American Psycho' on Tom Cruise. Bret Easton Ellis, who wrote the book, also said he considered Cruise an influence. Makes sense.
Uncle Sam was inspired by Samuel Wilson, a meat-packer who sold his product to soldiers during the War Of 1812.
Norman Bates, Leatherface, & Buffalo Bill
Movie murderers Norman Bates, Leatherface, and Buffalo Bill were all based on one serial killer: Ed Gein. Gein is notorious for murdering his victims and keeping the cut-up pieces of their bodies around his farmhouse. When investigators raided his home, they found, among other things, “four noses, nine masks of human skin, a lampshade made from the skin from a human face, and a belt made from human female nipples.”