Of course, it it was my call, I would go a completely different direction by making it a sequel of sorts (as opposed to prequel). It would go something like this:
Set after the events of X-Men 3, the presence of the 'cure' has increased human-mutant tensions with the public now convinced more than ever that the X-gene mutation is a disease which ought to be cured. Enter
Matthew Risman, an anti-mutant zealot who leads a group known as the Purifiers. It is his belief that the cure is a miracle by God, an opportunity to repent for the mutant/sinners and that those who refuse it are the Devil's agents. Hence, it is his belief that the remaining mutants need to be exterminated.
In these dark times, the X-Men have become the focus of the anti-mutant sentiment. Fearing that the school, and thus the children would be in danger with their presence, the main X-Men team now operate from elsewhere in hopes of diverting the dangers away from the school. Meanwhile, Storm (can be replaced by another character) has taken the role as headmistress at the Xavier Institute. She hires Emma Frost, the sole telepath strong enough to use Cerebro after Prof. Xavier's death, to help locate new mutants. However, this move proves problematic as Frost was a Magneto supporter who thus influences the students to take a more 'proactive' stance against mutant haters.
As the movie progresses, Storm and Frost come to loggerheads over a particular group of troublemaker mutants due to their opposing philosophies. Meanwhile, Risman and his Purifiers carry on their crusade, finding their next target in the children of the Institute.
As for who the central characters, my pick for the team is as follows:
Julian Keller/Hellion: A charismatic, self-absorbed mutant with the power of telekinesis. He's the 'leader' simply because he's the most goal-oriented. Has an antisocial streak and swayed towards Frost's world view. He and his group are generally seen as troublemakers/ rebels by the rest of the student body.
David Alleyne/Prodigy: An outsider to the group. Hellion's roommate with the power to steal other people's skills. Rational and attempts to keep Hellion's group from jumping into the deep end.
Noriko Ashida/Surge: An impulsive Japanese mutant with the power to absorb and discharge electricity. More reckless than Hellion.
Sooraya Qadir/Dust: A quiet Sunni mutant with the power to turn into sand. Afraid to speak her mind. Part of Hellion's group simply because they are the most receptive whilst she is ostracized by others due to her clothing.
Laura Kinney/X-23: A 'lone wolf' mutant with claws and a healing factor. Described as Wolverine's 'sister'. Has bloodlust issues which make people around her nervous.
Victor Borkowski/Anole: Wisecracking but fiercely loyal mutant with a reptilian appearance and the powers of camouflage and limb regeneration. Hellion's confidante. Panics easily.