Take The Amazing Screw-On Head. Adapted from a one-shot comic by Hellboy creator Mike Mignola about a Civil War-era android that answers directly to Abraham Lincoln, Head investigates ye olde paranormal phenomena with an assortment of bodies that his head screws into. (Mignola's original concept was: "makes a cool action figure.") His comrades are an Alfred-esque manservant named Mr. Groin and a stuffed dog. His arch nemesis is the droll Emperor Zombie. Other villains include vampires, werewolves, more zombies, and Ancient Evil -- all in the one issue.
That's a good premise for a comic and a great premise for a cartoon. The show was made for the Sci-Fi channel without further assistance from Mignola, and Korean animators put his singular art style into motion. Paul Giamatti voices Screw-On Head, David Hyde Pierce is Emperor Zombie and Molly Shannon plays their vampire love interest. I respect them all the more for lending their talents to a basic cable cartoon.
If the creators didn't appreciate or understand the source material, all the Korean animation and famous voice actors in the world couldn't save AS-OH. But magically (or so it seems after enduring so many bad comic adaptations), the cartoon mimics the comic's formula enough to serve as a start for a series.
AS-OH is a cartoon in the Saturday Morning vein rather than what the kids today see on Cartoon Network or Adult Swim. Instead of irony or gross-outs, there is physical comedy (a la recent Disney movies) and the inherent humor of hearing over-the-top-dialogue delivered deadpan. It's also educational: The pilot ends with the real origin of the Homestead Act. It's a good show, or would be, and I say that after viewing it in the present day instead of through the nostalgic glaze of hazy memories of TMNT and The Real Ghostbusters. Presently, Screw-On Head, the cartoon, only exists as a one-shot DVD; it's suitable mostly for people in arrested development who enjoy being frustrated.