Well if it weren't for that rule about no mixing of casts, I would write a book about a Federation Civil War. It would, naturally, feature a debate about the rights of individual star systems verses the Federation government. In this case, the Federation is unwilling to allow them to secede, either because of their location or because of some rare unobtanium resource that the systems possess. The systems could also be tired of paying all the 'taxes' that are necessary to sustain the replicator economy and want to shift to a more normal economic system.
The Federation government, meanwhile, simply refuses to understand why anyone would want to leave the 'paradise' that is the Federation--this was already their attitude toward the Maquis.
This story would, of course, be set after the Dominion War and so would have Starfleet also starkly divided between the Militaristic and Exploration factions and the Militarists are still, by and large, the ones in control. But even many of the Explorers are still siding with the Federation, they're just divided about what to do.