The thing I don't like - but it is dictated by the nature of it being a game - are the multiple wars. I'd rather see a future where the Federation peacefully absorbs all of its neighbours and grows to encounter the next cycle of angry powers (e.g. Fen Domar, Hirogen, Vomnin).
This please. I agree with Christopher
that the Vomnin aren't exactly angry, but they certainly could produce dramatic stories if they interacted with the Federation on a larger scale. I think we're not that close to seeing much of the Hirogen yet, but I'd love to see the Fen Domar.
I'd also love to see more of the Carnelian Regnancy and especially the Sheliak. [EDIT: Also, the Grigari and the First/Fesarian [!!
!!] Federation, both of which were name-dropped by Mack in Silent Weapons
, I believe.]
I mean, look at how the US's diplomatic relations have changed over 250 years: our first foe, Britain, is now our strongest ally. And other countries that were once diametrically opposed to us are now stalwart allies (such as Japan and Germany). On the other hand, our relations with China (which can't really be described as being positive overall) are much younger. It would make sense for the Federation to eventually make peace with its current neighbors and move on to new ones.