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Frame by frame is better and gives better more life like results. Plus facial animation can only really be done frame by frame.

Facial Animation

If you're animating in a program like flash or toonboom then you can cheat by using 'tweened' animation. This is a process that has been around for decades by adding a peg and moving that rather than redrawing the image.
The problem is this doesn't let you have really fluid movement. This is a very quick animation using pegs for movement:
http://www.youtube.com/watch?v=SBkHVNayq VI
You're better blocking out your animation and drawing as many frames as possible to make it move correctly