Ocean of Night Series by Gregory Benford. No particular order for these except for this one, which is definitely number one. A practicing astrophysicist who writes excellent hard sf and a voracious reader and lover of actual littriture, Benford remains my sf role model.
The Foundation Series. Surprise. More on Asimov (canonical and non) here and here.
Roadside Picnic, the Strugatsky Brothers. One of two non-Americans on my list (I'm sure I'm missing some); what I liked about the work was the very real-feeling, petty motivations of the characters and the abject alienness of what they were encountering. Benford has said that rendering the alien is the holy grail of sf, and even he sometimes falls prey to a need for making buddy-buddy with the aliens his characters encounter. That does not happen in this book, which is both part of its point and for me part of its appeal.
Neuromancer, William Gibson. Again big surprise. Visiting Chiba a few years ago I was disappointed that the sky over the port was, in fact, a nice January blue with some clouds. You could even see Fuji.
The Forge of God and Blood Music, Greg Bear. The Forge of God has Big Ideas and tells a Big story about as well as any science fiction novel I've ever read (while I'm at it, the wildcat book-trailer for Eon below is pretty cool too). Bear's Blood Music is a work that starts out as almost a techno-thriller but quickly moves into questions of consciousness and eschatology. Plus it takes place in the biotech area of San Diego, which of course is awesome.
Years of Rice and Salt, Kim Stanley Robinson. Hands-down the best alternative history work ever written, which I was fortunate to be able to tell KSR directly, and he confessed it's one of the books he's proudest of having written (and I can see why). My obsession with alternative history is ongoing (here or here for starters.)
Anathem, Neal Stephenson. Effectively, an alternative history of philosophy, for which music was written (see trailer below). As an aside, medical school has had the unwanted effect of making me impatient with fiction ("goddammit, why am I wasting time reading about characters that don't exist") so writers who wear erudition on their sleeve and info-dump, like Stephenson, are just fine with me. I turned pages because his re-imagining of the intellectual timeline was forcing me to make connections I hadn't made before.
Ray Bradbury, Fahrenheit 451. I've read this three times at ages 12, 17, and 25, and (the following is a true compliment) like a Bugs Bunny cartoon, you get more out of it upon successive viewings at more mature ages. Incidentally this level of detail is part of how Bradbury defines literature in the book, in a much-overlooked monologue.
Tlon, Uqbar, Orbis Tertius, Jorge Luis Borges. Borges is usually not thought of as being in the science fiction canon, and it's a short story. But the story plays densely with ideas (and frankly ignores characters) in a way that is most familiar to science fiction readers. It's a great science fiction story.
Urth of the New Sun, Gene Wolfe. Main argument: I mean come on. Also militating in favor of my inclusion of Borges on this list, try to tell me that the blind librarian right at the beginning of Shadow of the Torturer isn't Borges. The books take place in future Buenos Aires for crying out loud.
Ringworld, Larry Niven. My favorite hard science fiction. Engineering thought experiments.
You will note a lack of fantasy novels. Fantasy is transparently Northern Europe's early medieval period with different names (no surprise that genre-founder Tolkien's day job was scholar of Germanic and Old English poetry). But in the past few years I've read at least one fantasy novel that I really appreciated, China Mieville's innovative and political-allegory-dense The Scar.