That's a good point and a major issue. As with film-to-game adaptations, there's a danger of cutting and pasting the art direction rather than doing the source material full justice. On the topic of 2000AD, MadWorld is a title with an approach to art and animation that would fit the bill. Perhaps it's studios like Sega and Capcom, those willing (and able) to take more risks with IP that should be lining up alongside comics giants and their weird and wonderful designs/ideas.

Moore's Top 10 is a great off-the-wall choice. As a sandbox it'd be Crackdown meets Oddworld with a sprinkle of SWAT. How about The Ballad of Halo Jones? A space-bound road-trip through some creepy stellar back-alleys - think Beyond Good and Evil, with more post-punk feminism and less photography.

Brian K Vaughn's Y: The Last Man might make a similarly interesting (albeit difficult) transition to games. Titles with such long, rich runs as Preacher and Y are story boards in waiting, the challenge is keeping the heart of the original story beating whilst providing enough discourse for the user to remain interested without cheapening the material (interactive graphic novels; no thanks). The 2005 THQ Punisher title released for the Xbox is an example of taking a potentially serious theme - revenge - and rendering it impotent with a childish attitude to violence and cheap thrills.

That would depend on your definition of "transcend... on a mass scale". The commercial (and critical) successes of comics-to-film adaptations like The Dark Knight, Iron Man and even the X-Men franchise suggest that there's a worldwide, mixed demographic out there willing to pay premium cinema prices to watch comics characters brought to life (The Guardian's film editor went as far as calling Batman the Hamlet of our age).
The huge resurgence of interest in science fiction, fantasy and comics was highlighted this past week on BBC's Newsnight Review (Kevin Smith and Mark Millar made appearances).

Or how about The Mist? I can't think of any other premise that would stretch the survival horror template more than a single area/room setting, forcing devs to look to the writers for some resonant characters to drive things onwards.

I agree with the route of using the setting rather than the complete structure - the fact we probably know the ending to classic works would be a hurdle otherwise. Overlapping would a neat trick - imagine coming across a first-performance of a Shakespeare in a period MMO, or passing Nelson's ship as a prisoner bound for murky waters. Intertextual referencing is something rarely done in games (outside of their own cannon).