Federation post-apocalypse. It's all got to fall apart sooner or later... I'd like to see what the Alpha Quadrant will be like after everything has gone to hell, and how it'll be put back together again.
Sort of like Andromeda...
What I want is a post DW series showcasing the Federation struggling to put itself back together, facing resource problems, political questions stemming from some of the more "grey" things it had to do to win (such as lying to the Romulans).
I'd highlight the differences between the "core worlds" (the "saints in Paradise", to put it as Sisko did), and the border/colony worlds and how those differences complicated matters. Just to keep it interesting, I'd even throw in the Typhon Pact from the books.
On the production side, I'd like Manny Coto as showrunner, and the Reeves-Stevenses as head writers. They had Enterprise going in the right direction, and could have gotten it to 7 seasons if Les Moonives hadn't dropped the hammer on it.