"Space: the final frontier." Sounds a bit short-sighted, doesn't it? I mean, no offense to the ghost of Gene Roddenberry, but we've barely scratched the surface of what's out there beyond our atmosphere. To claim that it is the "final frontier" to be explored, charted, and colonized may not be entirely accurate. But, it does make for a catchy slogan and a great series of TV shows, movies, and games (ok, games... historically, not so much).
Thus far, "space" may appear to be the final frontier in MMOs as well, but to claim it as such is also short-sighted. The creativity of the human mind is a great thing. I'm sure we'll conjure up some novel concepts or twists on old themes or settings and make them work. The two biggest MMO sub-genres so far are undoubtedly Fantasy and Science Fiction (often space-oriented). Superhero MMOs are making a run for it and so are MMOs in post-apocalytic settings. There are even a plethora of oddly-themed kids games too.
Are there any genres we haven't thoroughly tapped yet? What about Horror? Mystery? Crime? Modern warfare? As for settings, what about Earth present? Earth historic? Alternate dimensions? Fairly tales? What genres and settings are you itching to explore?