Here's a list of what's been nominated so far, just to tidy things up. I hope I haven't missed any. Feel free to add your votes for this or that, and add new titles which are fantasy and science fiction must-reads (Needless to say, my list here does not count as votes!).
Remember, the number of people speaking up for a title is what matters.
Douglas Adams, The Hitch-Hiker's Guide to the Galaxy
Isaac Asimov, Foundation
Isaac Asimov, I, Robot
Robert Asprin, Thieves' World
Margaret Atwood, Oryx and Crake
Margaret Atwood, The Year of the Flood
L. Frank Baum, The Wonderful Wizard of Oz
Ray Bradbury, Fahrenheit 451
Ray Bradbury, The Martian Chronicles
Ray Bradbury, Something Wicked This Way Comes
Edgar Rice Burroughs, The Land That Time Forgot
Edgar Rice Burroughs, Martian series
Edgar Rice Burroughs, Pellucidar
Octavia E. Butler, Dawn
Octavia E. Butler, Wild Seed
Orson Scott Card, Ender's Game
Lewis Carroll, Alice's Adventures in Wonderland
C. J. Cherryh, The Chronicles of Morgaine
Arthur C. Clarke, Childhood's End
Arthur C. Clarke, 2001: A Space Odyssey
Michael Crichton, Jurassic Park
John Crowley, Aegypt series
John Crowley, Little, Big
Stephen R. Donaldson, Lord Foul's Bane
Arthur Conan Doyle, The Lost World
Harlan Ellison, Dangerous Visions
Harlan Ellison, Deathbird Stories
Carol Emshwiller, The Mount
Philip José Farmer, To Your Scattered Bodies Go
Alan Dean Foster, Icerigger
Neil Gaiman, Sandman
William Gibson, Neuromancer
Tom Godwin, The Survivors
William Goldman, The Princess Bride
Joe Haldeman, The Forever War
Robert Heinlein, The Moon is a Harsh Mistress
Robert Heinlein, Starship Troopers
Robert Heinlein, Stranger In a Strange Land
Robert A. Heinlein, Time Enough for Love
Frank Herbert, Dune
Homer, The Odyssey
Robert E. Howard, the Conan series
Aldous Huxley, Brave New World
Diana Wynne Jones, The Merlin Conspiracy
Stephen King, The Dark Tower series
Stephen King, The Eyes of the Dragon
Katherine Kurtz, Deryni Chronicles
Tanith Lee, The Silver Metal Lover
Ursula K. Le Guin, The Dispossessed
Ursula K. Le Guin, The Left Hand of Darkness
Ursula K. Le Guin, A Wizard of Earthsea
Fritz Leiber, the Fafhrd & Gray Mouser series
Madeleine L'Engle, A Wrinkle in Time
C. S. Lewis, The Lion, The Witch and The Wardrobe
Stanislaw Lem, Solaris
Sergei Lukyanenko, Nochnoi Dozor (The Night Watch)
George R. R. Martin, A Song of Ice and Fire
Richard Matheson, I Am Legend
Dennis McKiernon, the Mithgar series
China Miéville, Perdido Street Station
Walter M. Miller, A Canticle For Leibowitz
David Mitchell, Cloud Atlas
L.E. Modesitt, Jr., the Saga of Recluce series
Elizabeth Moon, The Deed of Paksenarrion
Michael Moorcock, the Elric series
C. L. Moore, Shambleau and Others
Larry Niven & Jerry Pournelle, Lucifer's Hammer
Ben Okri, The Famished Road
George Orwell, 1984
Tim Powers, The Anubis Gates
Terry Pratchett, The Colour of Magic
Terry Pratchett, Hogfather
Terry Pratchett, Reaper Man
J. K. Rowling, Harry Potter and the Philosopher's Stone
Brandon Sanderson, Mistborn: The Final Empire
Robert J. Sawyer, Calculating God
John Scalzi, Old Man's War
Mary Shelley, Frankenstein; or, the Modern Prometheus
Dan Simmons, Hyperion
William Sleator, House of Stairs
E. E. "Doc" Smith, the Lensman series
Neal Stephenson, Anathem
Neal Stephenson, The Baroque Cycle
Bruce Sterling and William Gibson, The Difference Engine
Mary Stewart, The Crystal Cave
Bram Stoker, Dracula
Theodore Sturgeon, Some of Your Blood
Theodore Sturgeon, Venus Plus X
Jonathan Swift, Gulliver's Travels
James Tiptree, Jr., Her Smoke Rose Up Forever
J. R. R. Tolkien, The Hobbit
J. R. R. Tolkien, The Lord of the Rings
J. R. R. Tolkien, The Silmarillion
H.G. Wells, The Time Machine
T.H. White, The Once and Future King
Jules Verne, 20,000 Leagues Under the Sea
Scott Westerfeld, The Succession
Virginia Woolf, Orlando