Shatner felt at one stage during TOS, that he was no longer the star of the show... because of all the attention Nimoy was getting. Depends on how the alien is written and how the actor performs in that role. I don't think a series necessarily has to have a human lead character. That person may have to be seen through the eyes of the crew under him certainly, and that alieness seen from our "normal" perspective.
Jeffrey Combs practically stole the show anytime he appeared on DS9 and ENT. God knows what would've happened if he'd been Shran full-time, assigned onboard the Enterprise and butting heads with naive humans around him, having held the most senior role aboard a starship himself. There's a two-way exchange going to happen, I suppose. New tricks being learned by an old hand. Then times when there's some "I told ya so..." going on.