Welcome to the Microscope fun
@Zantan
@ejnotts I guess it depends on your group and what you are planning, for just a couple of sessions type one shot or a quick game of something Microscope might be overkill, but it was with my very regular group of best friends and planned for the start of a 'big' campaign. Mileage always may vary with players... It's also just a fun game on it's own, so you could play it through once or twice to try it out ahead of a planned campaign creation kind of game.
I've found the pay off great, everything Zantan mentioned applies. You can cut play time down a lot if you skip over the roleplay, but then you can lose some of the dramatic impact, depends on your group I guess, not everyone is happy improvising RP scenes.
For pay offs, my main favourite has been, long story short, we had a villain in the Microscope game that used rabbits to spread a plague, so as time progressed rabbits were hunted pretty much to extinction. When they were camped for the night and those on watch saw a rabbit... Seeing your adventurers react to a bunny like its the one out of Monty Python is priceless! That villain is going to come back, and I'm working hard to kind of make it their fault. The look on their faces when they hear his name will be amazing!
We were also planning to use the Followers and Strongholds book to create a base of operations. They explored an old Empire watch tower which has a secret emperors magic laboratory with a teleport circle (a major thing as in the microscope game we made flying ships to get everywhere and made teleport magic all but lost to the world). The ended up going through it, but managed to get back and told me they were setting up shop in the tower. I looked so surprised because for some reason I had not planned it at all as a likely home base location, I had just thought it was a cool encounter location... Sometime you just miss the obvious...
I've not tried incorporating a setting, but you could easily use the main elements of it to establish the Yes and No parts at the beginning (what we are good to have and not good to have in the Microscope game) and use Microscope to explore areas and events. You could make a list for people to pick from as a focus list of ideas to help people out. You can always drill down deeper with Microscope or add more events in-between others. Time is mutable...
We have not tried a mid-campaign game of Microscope, we just had so much stuff from the first one, but I could see how much fun that could be after playing in the world for bit to go and flesh out some history some more.