A few lesser known gems:
Chronomaster is a unique sci-fi/fantasy adventure written by the late Roger Zelazny (whom I myself am unfamilliar with, but apparently his works are moderately famous). You go around several "pocket universes", each with their own unique setting and natural laws trying to remove them from stasis and discover who is behind it. Features the voices of Ron Perlman and Brent Spiner.
Normality is a humorous semi-sci-fi fully 3D (sprite-based, mind you) first-person adventure game set in the gloomy Neutropolis, where happiness is a crime and the dictatorial Paul Nystalux and his oppressive Norm Trooper cops rule all. You set out to join the rebellion to overthrow him. A very unique plotline with some great gags.
And last but not least, Toonstruck, featuring a live-action performance by none other than Christopher Lloyd, who play Drew Blanc, a down on his luck animator who gets sucked into a wacky world of his own creations, where he must save the kingdom of Cutopia from the vile Count Nefarious and his Malevolator. Features gorgeous cartoony graphics and humor and tons of familliar voice actors, not to mention the wacky puzzles and an unfortunately unresolved cliffhanger ending.