I've actually been thinking this for a little while. Having a smaller group of main characters with a broad range of secondary actors can have a lot of benefits. We can all think of characters who never clicked through most of their time on their shows (I don't want to mention any names in particular so as not to be rude, but I'm sure everyone can think of a few). I think this can happen for a variety of reasons, but usually its a combination of an actor not being all that great with writers who struggle to define the character.
To a certain extent there is a symbiotic relationship between writers, actors and characters. When actors exceed their expectations, they're given more opportunities to star in their roles and writers want to spend more time writing them. When actors fumble their role or are just bland, writer's are less enthusiastic in giving them much role in their scripts, and if a writer has a great script idea that he's really proud of, he's more likely to give one of the actors he feels will make his script shine in the lead rather then one who has under-performed. As an example some writers have noted that during TNG they liked to give really technically difficult lines to Levar Burton because they knew that, no matter what it was, he would make it sound convincing and real. That increased his exposure and meant he was often involved in plots with complex scientific plotlines that weren't necessarily engineering related.
On the other hand sometimes writer's just can't figure out how to make the character work despite the actor being solid. And there have occasionally been characters who were not nearly as strong early on because of that. Sisko is a good example of that, I think. In the first few seasons several of the writers admitted having a hard time with the character, until they latched on to the idea that he was at his heart a builder and that his strengths were a bit different from the Captains who came before. Until that point Sisko wasn't really the focus of the show, with a lot of the other characters having much more to do. Once they found that Sisko's role became much more central and there were more episodes focusing on him.
Either way, I think honestly being an actor on Star Trek is a much harder task then being an actor on almost any other show. Most actors know what a detective or a Doctor acts like. Before they ever appear on the show they've probably seen the role played thousands of times. Not many would come in prepared to be a Warp Core Specialist born in the 24th Century. I think that's why actors with a lot of stage experience are so successful on Star Trek, especially those who have done a lot of Shakespeare. What could be better training for Star Trek then learning to act using highly stylized language in a world and a role that is quite foreign to anything you're familiar with?
Which is why I think concentrating on getting a really solid smaller cast (five sounds good to me, but more or less would work) and a large supporting class would be the way to go. You might pick up a good actor who simply can't handle the stylized Star Trek dialogue and sound natural, but if he's a secondary character, who cares? You can try someone else out the next time. DS9 is actually a good example of this. There were two Vorta shown on DS9 that preceded Weyoun; Eris and Borath. But once the writers saw Jeffrey Comb's impressive performance on "To the Death" they brought him back quite literally from the dead, coming up with the idea that the Vorta were all clones so they could keep him on as a secondary character. Obviously there were other Vorta after him, but he became the face of the Vorta appearing in 24 episodes and having six different iterations.
That's the kind of luxury you have with secondary characters that you don't really have with primary characters who have signed long contracts. You can find actors and characters that really mesh and add a whole layer of complexity to your universe as you go along rather then committing to a character for the next seven years and hoping everything works out for the best without seeing them appear in a single episode as that character. Because once you have a primary character, you have to find something for them to do in just about every episode just to justify their paycheck.
The risk of course is that you find a great secondary character and that actor then gets a better job because of the performance on your show, but I think it would be worth the risk.