A new setting which owes nothing to the FFE Charted Space setting. New aliens, new civilisations, ships which actually move in space, freed from the dependency of having to stick to inhabited star systems (such as my Rift Runners), and new assumptions for ship builds to be put into the next High Guard.
New modes of travelling - Stargate equivalents, space warps, Conduits, space folding Reality Drives, and a rewrite of some general assumptions about Starships such as no more dependence on wilderness refuelling due to them having streamlined Bussard Collectors.
Some rewrites and assumptions about character generation, too. Drop the Draft. Stop shoehorning characters into military careers. Make psionics less of a pariah's game. I don't care if all the kids want to end up playing Jedi. Give them what they want, or they'll find a SFRPG which allows them to be Jedi, like that SW game next door. Or they'll just jump back into the Hasbro game.