I’ve got to go with Rumiko Takahashi’s Maison Ikkoku. A great manga novel that took something like 6 years worth of weekly installments to come out. Human characters, a fine love story, actual honest-to-God character development (something notably lacking in most GNs, let’s face it), and uproarious humor from time to time. They’re currently available in 15 compilations from Viz comics. Worth it.
If I have to choose a sort of mainstream thing I’d have to go with either V for Vendetta or Cerebus: Jaka’s Story.
Watchmen
The Dark Knight Returns
Black Orchid
Kingdom Come
The Killing Joke
Arkham Asylum
The Watchmen is good.
The Dark Knight Returns is better.
The best however (even though it’s really a comic book series) is Cerebus the Aardvark - Church and State being the best parts, so far…
Agreed, except the Preacher is a comic book series. 
So what? Most of Dickens started out as a serial. 
therefore:
V for vendetta
The Friendly ones (Sandman)
A game of you (Sandman)
From hell (Alan Moore, like V)
And how about
Like a velvet glove cast in iron (Dan Clowes, Fantagraphics!)
Maus was deep; I can’t say I liked them, exactly…
I’m also surprised no one has mentioned the two books in the Mage: the Hero… trilogy.
Although I can’t for the life of me remember the name of the guy that wrote, drew & lost the rights to them.
And Grendel vs. Batman.
I don’t even know why I’m contributing (?) to this thread. But I don’t understand why the Preacher series shouldn’t be considered a “graphic novel.” It’s all one story, isn’t it?
I’d never seen the “comic” version (I live in rural Iowa, we don’t even get Archie) but I tracked down Gone to Texas because Joe Lansdale (currently my favorite writer) did the intro. I got hooked and have all of them, and I think they’re great.
So Preacher has my vote. Although it means nothing, since I haven’t read a single one of the other nominees. Ha!