A lot can depending what city you live in because if you live in a hub city for an airline it'll be a lot easier to find flights.
Like the last poster said the Southwest Visa from Chase is a great deal - the 50,000 mile offer after spending $2,000 in your first 3 months. There is a $99 annual fedd but that card will get you about $600 in free Southwest airfare.
https://creditcards.chase.com/a1/southwest/offer
Another good option is the Chase Sapphire Preferred from Chase. You can earn 40,000 Chase Ultimate Reward points after $3,000 spend in 3 months. Annual fee is waived the first year. What's nice about Chase Ultimate Reward points is that you can transfer them to a number of airlines including Southwest and United.
https://creditcards.chase.com/credit-cards/sapphire-preferred-card.aspx
The last one I like is the Barclay Arrival card which gives you 40,000 points after $3,000 spent in the first 3 months. Those 40,000 points are good for about $440 toward any type of travel expense on any airline, hotel, rental car ect.. Annual fee is waived for the first year.
http://www.barclaycardarrival.com/