EterRNA (reg. req) is a game, of sorts, that asks you to design complex new ribonucleic acid (RNA) molecules, with the chance to have your efforts synthesised by Stanford University. A successor to the protein-folding of FoldIt. There's some background info at the NYT.
Hetherdale is a full scale point and click adventure, for free. Don't forget to use the map option when it arrives in order to travel faster.
Hanamushi has been mentioned previously, but the artist's site has been redone as part portfolio - part surreal point-n-click adventure.
Metaplace Raph Koster's customisable, isometric, browser-based 3d environment has now entered open beta. caveats: Registration required, some Beta flakiness (previously)
Pepsiwhite It's a cheezy, calcium-fueled enticement, but the implementation is rather good. A single player 3d board game with a milky message.