Sandman is what got me into the graphic novels, and what made me fall in love with the Vertigo imprint. So I'm probably going to be the millionth person to recommend Sandman, Y: The Last Man, Preacher, 100 Bullets, Pride of Baghdad, etc etc etc.
DC wise, I'll probably catch some heat for this, but I HATE superman, even though I'm quite familiar with his story, supporting characters, etc. There was one graphic novel that stood out though: Red Son. The deluxe edition is coming out November 17th, well worth your $17. Its about Superman landing in communist Russia instead of Smallville, and that's all I'll say about it. Phenomenal story-telling, and great art! Also another one that's been recommended a trillion times probably, The Dark Knight Returns. On top of that, Batman: Year One, Batman: Knightfall series, The Killing Joke, Watchmen (this one changed MY LIFE!).
From Image comics, I recommend Spawn, although I haven't read anything in ages, I started that series when it first came out. Awesome art, great dark stories and characters. Also, probably for the millionth time, The Walking Dead. I was recommended this and finally years later I finally started reading the collected TPB's. Great story, and apparently its going to be made into a TV show on AMC! Also, I saw that The Darkness was recommended, and I second, or third, or whatever that recommendation! Very dark, humorous, great art. Also look into Witchblade, for they tie in sometimes.
Marvel... Ah, Marvel... What got me into comics, and reading in general. I remember being a horrible reader in 1st-3rd grade, until my mom bought me a stack of comic books from a garage sale, all classic 80s Marvel titles. I instantly fell in love and improved in reading, and the teachers seemed to notice. By 5th grade, I had a high school reading level. Because of comics. But I digress. X-Men: Age of Apocalypse is awesome. So is the Dark Phoenix saga! The House of M series blew my mind, LOVED that!