Seconded on Sacco. His other stuff is ace, too.
Thirded! Safe Area was one of the first, and still one of the best (of the few) graphic novels I've read. I work in a book store and, incidentally, as I don't normally work in the comics/graphic novel area, I stumbled upon this thing today:
The cover art and packaging piqued my interest, so I picked it up and read about a quarter of it on my lunch break, and so far I'm really digging it (it's remarkable how often judging a book by its cover works out for me). I feel dumb for not knowing anything about Cerebus before today. It's a big deal in the comics world.
Also, reading something written from a female perspective (Jaka, eponymous) is doing me some good. I don't do that enough.
*Edit - I've done a little reading now and, ironically (given my last statement), there's been a lot of controversy surrounding the author's views on the man/woman relationship and feminism. I'll keep reading...