This is probably going to be a difficult question to answer without a little more information. I think the biggest question is... what airlines fly the routes you need at the price you pay?
I'd personally say Southwest, but if your Southwest doesn't fly to the places you want to go then that's pointless. Can you achieve the companion pass? Is it even useful for you? Or maybe you prefer ULCC and Frontier is actually your speed. Maybe you live by a UA hub and typically have checked bags, then you'd probably want a UA card for the free checked baggage (but you still wouldn't want to pay for your flights with a UA card!)
Then you have the flexible currency cards with either 3x or 5x points on airfare. Each of these have their own pros and cons. Depending on your spending and other patterns a CSR, Citi Prestige, or Amex Platinum might be your best choice.