When you are first getting started, it is usually best to start with a goal in mind. For example, you want to go to Europe in 2013, or the Caribbean in 2012, and you want flights and hotels to be covered with points, or something like that.

Then, look at the different airline and/or hotel programs and see which ones would help you meet your goals. A good way to have more options is to get a card with flexible rewards like the Chase Sapphire Preferred that has Ultimate Rewards points and/or a card that earns American Express Membership Rewards. I would get a couple cards on the same day, but make sure you can meet the minimum spending requirement on all that you commit to so that you will get the sign-up bonus.

First, just meet the minimum spending requirements and then decide which card to use in a given situation based on if any of your cards offer a bonus on that purchase (like 2x gas, 2x groceries, etc.....). Good luck!