What happens when the masquerade breaks? A lot of vampires are in a lot of trouble, obviously.
Although as noted, it depends how and why the omnibreach happens, and how all-encompassing it is. “We know vampires exist because it was on the news!” is different from “We know vampires exist because every human can now sense them!”
Smashing a fundamental of a setting should be a big deal, the game before and after should feel very different.
After Darth Vader dropped the Emperor down that vent, what was there to do in Star Wars? See the Expanded Universe for various answers, none of them very satisfactory. Better to move to another part of the universe, like Knights Of The Old Republic.
And do you (can you) leave a reset button? Hard to do in this case, which is why the idea was only really discussed in Gehenna and Mirrors.
A smaller change that still affects the PCs heavily can change the game as much but be more reversible.
Stranding the Doctor on Earth with his TARDIS broken altered the format of Doctor Who for a couple of seasons, but then it was off again through time and space. Of course, a series all about time travel makes retconning very easy to excuse anyway.