The Crowded Sky
Humanity colonizes a few dozen worlds within a few dozen light-years with "Slow FTL" -- and a century or three later, discovers "Fast FTL". Suddenly, wildly diverse human cultures that had developed in comfortable isolation are now only a few days apart -- and humanity has run headlong into Galactic society, which treats species as a cultural whole.
It's a mix of the Cold War and the ultimate uncomfortable family reunion: that whole Heinlein rugged-individual thing, where if you can see the smoke from your neighbor's campfire, it's time to move on... but there's nowhere to move.
I actually ran a GURPS Space game in this setting, though I never had the PCs leave "human space" -- the contact with the Galactics was Happening Over There, of in the furthest reaches. The campaign was focused more on trying to bring the wildly divergent human cultures into some kind of unity that would be "presentable" to the Galaxy at large.
The campaign taught me a couple of hard lessons about GMing, though. One: people who think nothing of pouring through volume after volume of published game books won't take a few minutes to read a couple of pages of GM-created background material.
Two: some players don't want options. In that background material that (almost) nobody read, I made it clear that I wasn't just going to let people write up their characters -- I was going to let them create their entire planetary cultures out of whole cloth.
Of a group of six players, two people did that. One of them wasn't one of our regular group -- I dragged him in from the BBS because he'd come up with an interesting character background.
The rest? "Oh, I didn't feel like doing that. My guy's just from a regular planet."
A "regular planet".
What's a "regular planet"?
Cyberpulp: The Wrong Turn
At some point in the early part of the 20th Century, Humanity took a "wrong turn" in theory and technology. Earth scientists missed out on developing the theoretical framework that makes all of the classic miracles of pulp Sci Fi not only possible, but simple and cost-effective: gravity control, force fields, FTL travel, directed energy weapons and the ability to generate and manipulate massive amounts of energy.
Without this simple, basic theoretical keystone, Earth has spent most of a century refining what most of the galaxy considers a technological dead-end: the ability to manipulate miniscule amounts of power with great precision, using semiconductors and integrated circuits. The ability to perform massive calculations at high speeds -- in pocket-sized packages. The Galactics have building-sized "electronic brains", but Terran children play with shiny toys that have more raw processing power.
This kind of hardware doesn't play well with Galactic standard tech, however: GalTech pumps out the equivalent of an EMP pretty much continuously. Assuming that a Galactic culture even stumbles across the principles behind semiconductors and transistors, they have no real motivation for DEVELOPING it: GalTech is just too obviously useful to spend time playing around with fragile, low-powered curiosities.
As a result, Humanity has tools that most of the Galaxy finds just as miraculous as we find theirs.
The twist? We're not the first race to have gone down this road.
The others, however, have all vanished, within a century or two of their "wrong turn". Nobody really understands how, or why, or if they've all fallen prey to the same thing. The general assumption is that if an industrial culture doesn't develop the ability to expand off-world and to the stars, they run out of resources and destroy themselves fighting over the remnants. This doesn't explain the the worlds full of empty, intact cities, or the ones where no trace of cities can be found, or the worlds that have somehow vanished entirely...
Never got a chance to use this one. Might save it for The Great American Novel someday...