PCs snap into a new reality. They are far far from home, on a rocky outcrop above a field of mushrooms and strange creatures. Things don't work the same way they did back in the real world. Some weapons do nothing, others are insanely powerful, and spells don't work at all. Creatures and their behavior there make no sense; they may meet other versions of themselves, or forests where you're underwater when you walk in the forest, things like that. You can't keep them there for too extended a length of time (it'll be too unbalanced and not-fun if all their usual gameplay mechanics are just gone for an extended series of adventures), but maybe there's a type of crossroads with a massive six-legged bear-like creature who says if they each give him one thing that's most dear to him, he can give them directions closer to their home. The directions take them to some odd astral place that's at least in the sourcebooks (feywild maybe) and their stuff starts working again, so they can start working on how they might be able to get back to the material plane. If they don't wanna work with bear guy then they're going to be stuck in feywild-squared with weird stuff happening to them for potentially quite a very long time.

Or

Fire engulfs the whole stronghold, all of a sudden. Either the BBEG keeps fighting, invulnerable to it, or else gets consumed by it while the PCs have to flee for their lives like the end of Metroid, and the BBEG presumably perishes in the ashes. If you want to make them work for their treasure you can hint to them that they should go back and sift through the ashes and they might find some neat stuff that wasn't flammable.

Or

Anything the BBEG does to the players starts impacting one of the players (chosen at random) instead of the BBEG. BBEG can hurt them but chooses not to, instead invites them to keep hitting BBEG but they're only hurting their other party members and BBEG is fine. Once they stop hitting BBEG, BBEG gets really angry and starts chasing them out, telling them to get out get out get out. The next day they discover that they are still getting injured when stuff happens to BBEG, and the new quest is to either figure out how to undo the wish (nigh impossible) or else undo the insanity so that the BBEG will no longer have awful self-destructive things happening to BBEG which will then come back at the party.

Hope these ideas are somewhat useful