I'd have to go with Slaughterhouse-Five. I read it in my first year English class and I loved analyzing it so much that I credit it with my decision to make English my minor.
Honourable mention to Lolita, which made me feel all kinds of complicated and uncomfortable things and has stuck with me, and One Flew Over the Cuckoo's Nest, which combines two of my favourite things (literature and mental health) and spawned a pretty solid movie adaptation.
The Virginian-Horseman of the Plains by Owen Wister is among one of the oldest western stories ever written yet over the past one hundred plus years it has been the base for several long running movies and a television series. Each version is remade in its own unique way, but the original story line is still visible. http://diana-lee.hubpages.com/hub/Remak … -Virginian
I'm not sure if this qualifies, but The Time Machine by H. G. Wells had a huge impact on me. There were a number of classic science fiction and fantasy novels that seemed beyond me when I first got into speculative fiction, but the Time Machine served as a sort of gateway book that showed me the roots and value of genre classics.