Others may have other advice, but I would recommend either a Citi or Chase tandem.

Chase Sapphire Preferred ($95 Annual Fee) + Chase Freedom card (no annual fee):
The points from the two cards combine together, making it more practical than earning a lesser number of points across multiple loyalty programs. Use the CSP for Travel and Dining (which earns 2 points / $1), and use the Chase Freedom for the rotating categories (which earn 5 points / $1). Any spend that doesn't fall into a bonus, just put on the CSP to count towards the 7% annual bonus. Points can be transferred to airlines or some hotels, if that turns out to be the more valuable redemption method for your individual needs.

Citi ThankYou Premier ($125 Annual Fee) + Citi Forward (no Annual fee):

Again, the points combine. Use the Citi Forward on Dining/Amazon.com/iTunes/Movies (which earns 5 points / $1), and put the rest of the spend on the ThankYou Premier. Use the Premier for any airline tickets not purchased with points, in order to earn "flight points" which are automatically earned with matched spending in addition to the 1 point already earned (essentially making it 2 points / $1). Also, the companion ticket should save you more than the annual fee of the card, if you're traveling with family. Also, it knocks 15% off base airfare for up to 4 people an unlimited number of times, so that would also save you a great deal if the availability matches what you need. Otherwise, use the ThankYou points to book flights at 1.33 cents/point, or gift cards at 1 cent / point. Points are also transferable to Hilton.