Under a few circumstances, it could work, imo. The main concern being that it's the lead of the show
1, If the alien was only minimally alien looking, like a DS9 Trill
2. If the show were a spinoff, starring an earlier character becoming a captain, like for example Worf. We're familiar enough with him that he could take on a lead role, & his makeup would not be as much a difficulty to the audience
3. Perhaps if it were a long standing alien race that the audience is accustomed to, like a Vulcan. I'm thinking of Saavik, who when her hair is down, only really looks minimally alien, as I mentioned before
1. Makes sense, so as to not alienate any new viewers--though if they went with a Trill I think an Unjoined one would be better, they are supposed to be in the majority after all.
2. I could see that, though I would prefer anyone but Worf. Yes he was a good character, lots of development and storylines, Mr Dorn did an excellent job of bringing him to life, etc, but I think he's been overused and I don't think there's anything more to be done with him. Besides, due to his actions on DS9, Sisko said it was extremely doubtful that he would get his own command.
3. I would love to see a Vulcan as Captain, or maybe a Vulcan-hybrid. Saavik would kick ass! Would be good to see adventures in the early-24th century as well. Maybe she got command of the Excelsior
after Sulu was promoted to Admiral?