Most of the comics I read are Mainstream. It's just the stuff I dig the most. But there are oodles of great non-mainstream books out there. So TINA has recommended some for everyone (thanks, Tina!):
SCOTT PILGRIM: Cute & hilarious! There are fun gaming elements added in for extra added goodness.
PROFESSOR'S DAUGHTER: French GN just recently translated into English. The illustrations are lush & the story is sweet and kinda sad.
WORMWOOD GENTLEMAN CORPSE: Book about a zombie detective set in a supernatural world. Effing hilarious!
TEENAGERS FROM MARS: Old school classic. Just perfect.
BLACK HOLE: One of the creepiest books I've ever read!
PIZZERIA KAMIKAZEE: Wristcutters is based on this. The story is one of a kind & mucho interesting.
UNLIKELY: THis book sums up how people look back and remember relationships - scattered memories of the sweet, the shitty and the funny. Honest stuff here.
MOUSE GUARD: Gorgeous story of mice templar!
TANK GIRL: If you haven't yet read the Hewlett stuff, THEN scoop the new run by Ashley Wood. Fun shit in an adult-ish way. Random & strange.