I think it's easier to come up with stand-alone titles on the Sci-Fi side than the fantasy side, but even on the sci-fi side the pickings are slim.
Tigana, by Guy Gavriel Kay, as already mentioned, is a great fantasy novel.
Grass by Sheri Tepper is a great sci-fi novel.
Armor, by John Steakly is a fun (but certainly not well-written) sci-fi action novel.
Tower of Fear, a fantasy by Glen Cook (also mentioned already)
Michale Stackpole has several stand alone fantasy novels, unrelated to his works in established universes. Once a Hero is the best of these, and Talion is the only other one I can remember.
Nightfall, classic sci-fi by Isaac Asimov
There is No Darkness, sci-fi by Jack and Joe Haldeman
Buying Time, sci-fi by Joe Haldeman
I was going to add Forever War, sci-fi, by Joe Haldeman, but I see he actually wrote a sequel 20 or so years after it. How odd.