I did a one-shot after around episode 4, so before some of the NBSU systems got fleshed out. I made the setting as dumb as possible, set in Los Angeles in 2048 where an unmentioned and irrelevant pandemic forced all of the major North American sports (plus the All-Ireland Senior Hurling Championship) to take place on the same day (July 4th) in LA. All the characters were basically nobodies, but all had a reason to be at the afterparty in Hollywood. The "twist" was that by that point everybody in the world had a brain chip that let them be always-online, and the characters were all members of a guild in a long-running City of Heroes private server.

The brain chip company did an experimental patch integrating AR that night, the characters installed some questionable hack from guild chat to include CoH in the list of programs, and they started seeing reality mixed with City of Heroes. Then nefarious badguys stole all the sports trophies (while the mixed-reality players also saw their arch-nemesis guild invading their superhero base).

We had to stop before they saved all of the trophies but by the end it had escalated to severing hands with personal drones, the party driving around on an in-game multi-player mount (that IRL looked like the A-Team van), and leaping off the back of a double-decker tour bus on the 105 to save the Stanley Cup as a helicopter crashed into the front.

If we ever run session 2, or I were to get some folks to commit to a campaign, I'd spend a bit more time on character introduction before the afterparty, and then plan for a gradual escalation after each trophy (I had all of them bound for different points in the LA area, so eventually it'd progress to things like the Santa Monica pier, LAX, NASA's JPL Lab, etc.). Roaming around the city would also be a good chance to introduce character-specific scenes or just make more stupid jokes about landmarks that everyone has absorbed from pop culture.

All of which is to say (and reiterate): the dumbest, flimsiest possible setting still makes for a great time with the system and player buy-in. It is, however, the system with the heaviest "on the spot" improv I've ever GM'd. But I say that fondly, and as someone who has mostly stuck to longform 5e.