I'd like to see a game in the same vein as PS:T. What I mean by that is a game that tackles serious, philosophical issues (insofar as a game can do such a thing). The actual form is not important, although I would like it to be an RPG. Seeing as how Torment barely fitted in RPG conventions, it could just as easily be an adventure.
The details of the story are not important but it has to carry real weight and be closer to actual life than to arbitrary mechanics. Just like in Torment, which could be superficially labeled as bizzare or outlandish - but is really a very human story of duty and redemption. Hopefully it would be aesthetically appealing.
Things that popped into my mind while writing this suggestion: Tarkovsky's Stalker, Blade Runner, Gene Wolfe's Book of the New Sun, Shadow of the Colossus (for aesthetic reasons).
Keep it human and people will be talking about it for years, like they do with PST.
Good luck.
PS: It should not be PST2. That book is closed in the best way it could be, and there's nothing more worth saying about the Nameless One.