With my (late) first pick, in the American Lit category, I pick
Gravity's Rainbow by Thomas Pynchon.
The people who run
The Modern Word, a website about 20th century fiction put it this way:
Considered by most to be Pynchon's greatest work, Gravity's Rainbow is one of the most celebrated -- and notorious -- novels of the twentieth century. Crammed with countless allusions that range from rocket physics to pop culture, organized along a structure that satirizes the liturgical calendar while paradoxically drawing power from its symbolism, and stubbornly resisting any definite interpretation, Gravity's Rainbow has achieved the status of a postmodern masterpiece, if not a modern Moby Dick or Ulysses.
Gravity's Rainbow takes over your life, makes you crazy, has you seeing Them and Their Plots everywhere you look. It's a manual for the proper paranoid responses to a world which is sexually in love with death. It's also a musical comedy. The 1974 Pulitzer committee called it "unreadable, turgid, overwritten, and obscene". It made an illustrator named Zak Smith crazy enough to
illustrate every page. And it gave me a name to use as an internet handle. I love this book.