A campaign where characters are in a quantum leap type scenario and don't realize it going in. First session is normal. Generic D&D setting and basic quest like "Cultists of the Red Hand have kidnapped some people from a nearby village and King Harold has tasked your party with rooting them out from the nearby abandoned castle."

Next session, change the setting entirely and without warning, but keep the general details the same.

"Sheriff Harold has deputized your posse to round up the outlaws of the Red Hand Gang which has kidnapped several townsfolk from the nearby settlement. They're holed up in the old abandoned mine."

Next session, same thing.

"Grand Judicator Harold has contracted your team of specialists to rid the sector of the Red Hand Space Pirates who are holding a group of colonists hostage at a nearby abandoned station."

Keep changing the setting/genre every session, have the PC's be the only ones aware of the changes. Main storyline is figuring out who/what/why is causing the reality shifts and trying to get back to their own reality while still fulfilling the original quest objectives.

Settings start out predictable (Fantasy, sci-fi, western, etc) but slowly grow more unhinged (circus-world, cells in a body Osmosis Jones style, otherwise normal world but everyone is a fish in individual tanks piloting mechs, etc.)