Deciding on which major credit card company you want to go with might already be decided for you. Sad, I know but the benefits outweigh the risks.
What I mean by this is if you live in Philadelphia, PA you are going to have to pick American, as they have a major hub here in these smaller airports and it only benefits you if you have more opportunities to fly out during the day to a myriad of destinations.
Likewise, if you live in Denver you might be stuck with United or Frontier as your carrier.
If you live in Boston, you might want jetBlue. Or Delta if you live in Salt Lake City or Minneapolis St Paul.
But if you live in LA or New York, congrats you get to chose any of the big airlines as your major carrier.
It really comes down to who do you want to fly and when. Hopefully your favorite airline choices have lined up with where you have decided to live. Check out the Big 3 below, sorted by airline.