I think almost any scenario can work, if approached the right way. Looking at a time it didn't work and saying "Well, never do that again" just doesn't cut the mustard as valuable analysis. By that measure we should have a rule No More Women Commanding Starships
(if you don't like VOY).
Details. Tis all in the details. Consider the second season of Buck Rogers
for instance. One might easily look at its failure and conclude "Well, science fiction series aboard starships don't work." In fact I'll bet money some folks did say as much. You can point to Firefly
as evidence of a pattern. Nope. Series about starships. Don't work.
That being said "A lone remnant of Starfleet tries to preserve the idea of an almost conquered Federation" or "A space station in the Gamma Quadrant" or "A new dreadnought-class starship confronts the Morzak Imperium, devourers of the Borg" are really little more than a single seed in what needs to be a garden. To really judge an idea we need more details.