I've always liked the idea of a 3rd Generation in the Trek universe--something that takes place far enough ahead so that travel is no longer just limited to the Alpha and Beta quadrants, but spread out across the Gamma and Delta quadrants. At the end of DS9, the Dominion was largely held to a treaty with the Alpha quadrant, and by the end of Voyager, the Borg had been weakened, but not crippled. I think the obvious next steps would be a larger Federation including Klingons, Romulans, and Cardassians who then have to face a galaxy-spanning war between the Borg and Dominion. Something like that would keep the Federation far enough removed to still spend a lot of time on exploring while having a background on-going arc where Federations ships have to deal with accidentally getting caught between the Dominion and Borg, both of whom are largely indifferent to the Federation at this point, despite the added strength of the other three major races.

A set-up like this gives so much room for writing and drama. There's the obvious "meet new aliens, reach the new limits of the galaxy" stuff. There's a war arc. And there's plenty of room for shaky Federation in-fighting about "should we or shouldn't we" get involved in the war between the Dominion and Borg. It also puts two popular, ultra-powerful Trek factions directly face to face with new possibilities. Both the Borg and Dominion worked by largely just throwing more fighters at the problem, because individuals didn't matter. The Borg could be made to easily detect the shape-shifting Founders, and both sides could be desperately trying to curry some kind of alliance with the Federation to figure out a better way to fight than just throwing massive numbers at each other over and over.

This all just seems like the obvious way for the franchise to have gone. Enough with all the prequels already.