Depends where you are and what you want out of it.
Many of the cards that earn static points for "miles" (well, really it is a static credit), such as the Capital One Venture cards, are great for hotels and cheaper domestic flights, but are absolute horse shit if you want international flights, in particular international premium cabins.
American and Alaska have the best programs in the states for international travel redemption, so with that in mind, you could look at their cards. In addition, neither of those airlines has gone to spend-based mileage accrual, so if you do happen to fly a little bit, you can still get a healthy amount of miles. Pair that with a credit card and you can rack up miles in a hurry.
JetBlue and Southwest are great for domestic flights.