Here's what I would like to see...
A pair of "new mutants" from Xavier's school, caught up in some problems away from school, and saved by a man out of time, a lucky sharpshooter, (both former members of a mercenary group) and a sword wielding telepath who dresses in a skin tight leotard (I'll take her instead of Shatterstar or Feral)...
Here would be the team make-up:
For the bad guys, I'd like to see Deadpool as a hire thug, played by Ryan Reynolds (but he has to wear the mask, be able to talk, and break the 4th wall).
Of course he's just a thug (that could join the team in the second movie) hired by the real baddie...
The Friends of Humanity, or Selene, or the White Queen.
I think the Friends of Humanity make the most sense as I could see them hiring Deadpool to kill off his own kind. This would make Deadpool the main villain, but then we would also need a leader of the Friends of Humanity. How about Graydon Creed.
If we don't need to have Deadpool in the movie (maybe cause he's getting his own flick) then the White Queen and the Hellions would be perfect, and possibly have Fitzroy as a major climatic baddie that leads them to Selene in the second movie. The idea of an opposing team (the Hellions) led by the White Queen is amazing!