I know that 3e's rules were really amenable to creating stuff like alternate WWII scenarios, 1970s racing games, pirates, Saturday morning cartoon bands, and so on.
4e really seems to scream "this would be a great basis for superhero gaming," because of its focus on everyone getting an advance of powers, plus tactical awareness and use of terrain, but I can't really come up with any other possible stuff. What else do people think might be fun as alternative things to plug the rules into making? (This is just idle curiousity. I'm nowhere near professional enough to actually make and publish an alternative.)