Fixing some of the problems people had with X-Men: The Last Stand is the basis of what I would do with X4. The movie itself had potential, but nothing really panned out as well as it should have, mainly because of time and casting constraints, so the movie just ended up slightly choppy and half-assed.
First off, it'd be stated from the beginning that the cure was a hoax and its effects wore off after some time. Now, that doesn't necessarily mean that all the mutants got their powers back right away - in some cases, the mutants might have died due to complications with the cure. For the purposes of my story we would have Rogue, Mystique, and Magneto's powers restored to them, which I'll go into later on.
The cure business is what will get the plot from point A to B, because this new mutant crisis has forced the world governments to take a bigger role in dealing with mutantkind. The implications of that mean that Hank is out of the job, so as not to upset the general public by keeping "part of the problem" as someone who would be in charge of making decisions for the rest of the country. In response to this new anti-mutant sentiment, a cloak-and-dagger operation within the government is created to give the public a more positive view of mutants: X-Factor (consisting of Forge, Quicksilver, Scarlet Witch, Multiple Man, Mystique, and with Beast behind the scenes). This team would be very much like the Avengers are in the comics - they'd be paraded around in the public and be media darlings, in stark contrast to the outsider X-Men.
Back on the X-Men side of things, Rogue fell into a coma when her powers returned and she almost killed Bobby in the process. Bobby, Kitty, Warren, and Colossus are more or less the New X-Men, or the B Team in this movie, so all the while the senior members of the team (Storm, Logan, and the newly added Emma Frost) try to get to the bottom of some strange occurrences relating to the cure. This would bring them to the NY offices of Worthington Lab, where Warren's connections allow them to get a close look at what the cure was and what went wrong with it. They also get wind (possibly from Cerebro, or personal interaction with the mutant in question) that some of the mutants who the cure had further mutated (the Morlocks) were ambushed and nearly wiped out (think the Morlock Massacre).
This would bring them in contact with Gambit, who was being questioned at the scene of the crime (cameo appearance from Officer Lucas Bishop), who Wolverine has a strange connection with. They manage to take custody of Remy and hold him in the brig until he's ready to talk. Using his criminal skills, he escapes and stumbles upon Rogue, who wakes up working more or less on auto-pilot, with the previous people who she's absorbed coming back to the forefront of her personality and bringing their abilities with them. The B-Team immediately go after Rogue, as the others are already pre-occupied with one one thing or another.
Meanwhile, Hank and his team do their thing (and bump heads with the X-Men at several turns, even going as far as arriving at the mansion to tell them to quit while they're ahead, and leave the superhero stuff to X-Factor), and we see how Mystique and Madrox are working with the feds against their will (think Mystique and Sabretooth's roles in the X-Factor comic, where they were fixed with equipment to make sure they never step out of line), but they both do their jobs brilliantly, regardless. We see that Forge created most of the tech that the team uses, including their helicopters, the inhibitors that Mystique and Madrox have, along with some highly advanced weaponry that the government is commissioning from him.
Eventually we would have all the plotlines collide with the X-Men trying to get Rogue and her powers back in check, while X-Factor tries to stop them all from permanently ruining the reputation of mutantkind. There's more to the story, but since I'm planning on doing it as a fan fic (which I could post here if I ever finish it), I didn't want to give up everything right now. Magneto (who would appear in the opening scene to put any doubts of his regaining his powers to rest) and Xavier would cameo in the story and open the door for a 5th movie, but considering he was the villain in the entire trilogy, I wanted Magneto to take a backseat in favor of someone else.
A wordy first post, I know, but this is a story I've had building in my head for some time now, so I had to try and be as detailed as possible. Sorry about that

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