My vote goes to Worf. While he may not be the first candidate Starfleet-wide, he does have years of experience on the ship now, knows it well and also has both a great deal of tactical and diplomatic experience that would be required for the flagship. He's also likely the most marketable character from the current TNG crew.
Of the other characters mentioned in the posts directly above, I agree Sisko feels too small-universe, and not an ideal choice given his recent "instabilities"; he's just gotten settled on the Robinson
so I'd leave him there for a while yet. Kira has retired from service, and I don't see her returning unless there was some great threat that demanded her presence. And I don't see Riker leaving Titan
either. I suppose he could leave command to Vale and return to the Enterprise
with Troi, but that would not only make things awkward for Worf, but also leave behind the closely-knit crew he helped build on Titan
. I just don't see that happening.
If we do go for a new character, then yes: let it be an alien, perhaps also a woman. I've actually warmed to STO's Shon quite a bit during the recent updates, but we've already explored Andorian, Vulcan and to a lesser extent Tellarite culture quite a bit. My pick would be from one of the less-often mentioned Federation species, like a Benzite or a Denobulan. And if we do have to have a human, let it be one from a colony world.