Play in a corner. Your highest number should be in the corner, and your secondary big numbers should be either directly to the right or below your highest number. Example, if you choose the top left corner, the vast majority of your moves should be left or up. If you get "trapped" (can't move left or up) make a move to the right and see if you can QUICKLY gobble up some points. In this situation, be very paranoid. And do everything you can to get your main number back into the corner as soon as possible.
You do NOT want a two to be touching your big number. If it is, turn that sucker into a four ASAP.