with zero regard for the actual marketability of any of these games (most are pretty niche), here are the themes i'd personally love to play:
Mystery Science Theater 3000
Portal 1/2 (the GLaDOS callouts would be epic! and portals lend themselves perfectly to lots of VUKs and subways)
or ... how about Pinside Pinball? seems like there'd be a decent sized audience for that if the humor was done well! Moderator Multiball! Smack A Troll! timed 6-ball reverse-flipper "drunken posting frenzy" mode!