Arthur C. Clarke, Childhood's End, 1953, science fiction. Perhaps the greatest novel by one of sf's most forward-looking authors, with a daring vision of the possible end of the human race.
Isaac Asimov, Foundation, 1951, science fiction. One of the most influential visions of a galactic empire and its downfall in the history of sf.
Neil Gaiman, Sandman, 1989-1996, fantasy. Although serialized as a monthly comic book, this is in reality a cohesive, unified novel--an illustrated novel, if you must--about the power of stories to shape our lives.
Neal Stephenson, The Baroque Cycle, 2003-2004, fantasy. An incredibly ambitious alternate history involving conspiracies and codes and the place of science in human culture.
Philip Jose Farmer, To Your Scattered Bodies Go, 1971, science fiction. In the first book of the Riverworld series, every human being who ever lived wakes up on a new planet after their death.
L. Frank Baum, The Wonderful Wizard of Oz, 1900, fantasy. The fairy tale gets an American updating in one of the most referenced, parodied, and beloved books ever.