This is a great topic and some fantastic universes have already been mentioned here -- Vinge, Herbert etc. SF has most of the best ones IMHO -- Ursula Le Guin's stories in her Hainish Universe are really interesting, and Scott Westerfield has a fabulous set-up going on in his Risen Empire series.
Fantasy doesn't tend to fare so well on the originality front, but recently, I blogged about some of my favourites in a post entitled,
100 imaginary places to see before you die. Julain May, China Miéville, Robert Holdstock and others feature.