I see this summer's big DC Comics crossover is about how The Universe Is Slightly Different, complete with one hero being the only real-universe person to know what's wrong and that it must be fixed.
Not the same as The Evil Mirror Universe, The Universe Is Slightly Different lets you rearrange characters, resurrect dead ones (and kill off current ones) with abandon, try out variant power sets and team combinations and costume designs and show a bunch of What If...? ideas all at once and possibly interacting. It lets minor characters take the spotlight in ways they never normally would, allows a bit of experimentation by players and GM, can possibly leave some aftereffects when everything else goes back to normal if an interesting enough idea comes from it, and generally ends with a big battle with not the normal sides fighting each other over the reality-fixing MacGuffin.
It can certainly make for an interesting session or two of a weird enough ongoing game. Players get to play other ideas they had for their characters, or ideas you had for them (which you should discuss with them first) and ideally somebody gets to freak out about how much better their alternate life is. (Last time Marvel did this with House Of M, the trap was that everyone's life was better.)
I admit I love this. Did it in The Watch House as well as a parallel universe and a Days Of Future Past post-apocalypse nightmare world and a fairytale land and a fourth-wall-breaker and a time warp. (And I'll note that Supernatural has done more than half of them since. Nice to know I have fans...)
About the only obvious ones I missed were "the Nazis went back in time and won WWII!" (which would be a bit off-topic and I already got Milli to fight Nazis once) and "the secret magic is out in the open so the heroes are famous!" (which... hmmm...)
Any game with a sufficiently high Weird Level can benefit from occasionally looking sidelong at it, asking what the essentials of the characters and setting are, and what happens if you change some of the details.
For added amusement, the "one hero being the only real-universe person to know what's wrong and that it must be fixed" can be the only player who doesn't get advanced warning of the change, if you trust your players not to mind the temporary bait-and-switch and to go along with the joke.