My personal pick would be Absalom, Absalom! by William Faulkner. Thoroughly impressive and often difficult, this book feels natural, inspired, and almost incandescent with verve. It's a book that lives - a dark life, but it lives - and it is very re-readable.
The structure is interesting and good, with multiple narrators telling different parts or different versions of the same story. The characters are, I suppose, not completely differentiated, but that is due to the "told story" nature of the novel. Given this caveat, the characters are still interesting as individuals and in relation to one another. (In a post like this, regrettably, there's no time to go into details.)
The story resists complete exposition or resolution. A mystery stands at the center of the text. This is a powerful element of the book, for me, because it seems to be a commentary on the nature of truth and experience. No matter how often we re-tell a story or re-live a moment, the truth of it - the meaning - remains elusive.
Some other contenders: All the King's Men; The Brother's Karamazov; Anna Karenina; Giovanni's Room; Tropic of Cancer; The Great Gatsby; The Stranger; Waiting for the Barbarians; Sun Also Rises.
These books achieve different things, technically, formally and artistically, but they are each truly great in my estimation.
I'm sure you'll get quite a range of responses to this one!