A lot depends on what you want, how much you'll spend, etc. Many people (including me) like the Starwood Preferred Guest American Express card. No annual fee for first year, and only $30 after that. You can use Starpoints for hotels, or transfer to airlines. The Hhonors Amex card is also good, and has no annual fee.

Some like the Delta Skymiles Amex card - they often give double miles, but have a larger annual fee.