Transhuman Space + 2300 AD

I think a mashup of Transhuman Space and Traveller: 2300 AD (later 2300 AD) would work quite well. They both share the trait of being relatively "hard sci-fi" rpgs. Both eschew world governments and the like for squabbling nation states continuing into the future. Both try to avoid most of the fantastical technologies of a lot of space opera.

There are a lot of differences, sure, but I feel like those differences could compliment each other. Transhuman Space's exuberant optimism regarding AI and biotech balances out 2300 AD's in places laughably conservative (and now dated) notions regarding future tech. Adjusting in the direction of 2300 AD's temporal setting (maybe meeting in the middle at 2200) would make Transhuman Space's rosy tech and space travel outlook look more conservative. Bringing in 2300 AD's stutterwarp drive and "realistically alien" aliens broadens Transhuman Space into interstellar science fiction, which is often more to the rpg crowds' liking than solar system-confined post-cyberpunk, while staying relatively true to the hardish sci-fi leanings of TS. Plus, 2300 AD has a star map and young space colonies ready for you.

Of course, you could do without FTL and keep 2300 AD's aliens and colonies. If you had things like Alastair Reynolds' "lighthuggers" and suspended animation sleep, you could still maintain 2300 AD style civilization, particular when you factor in Transhuman Space tech regrading brain downloading and bioroid bodies.