If you haven't already noticed, there are a lot of opinions as to what's best. However, the best advice so far is to handle as many as your local gun dealer has in stock. There's still no guarantee it'll work for you even if it fits one person's hands here and their reason for owning it.

Assuming that "defense" is probably high on your list of potential uses, reliability is essential. Beyond that, also look at the features. Some people prefer having an exposed hammer. Some DAs can be decocked, either by a dedicated lever (i.e. Sig) or through the safety (Beretta). Some people like the feel of polymer frames, others hate them. Some come with night (tritium) sights, others don't. Some magazines are harder to find than others, and often considerably more expensive. Plan on mounting a light or light/laser combo? - probably want to have something with a Pic rail. Holster availability?