I've played about 4 hours of the game now--great experience so far. They've done a great job of updating the Fallout series--it's got the same feel and familiar game play, but wrapped inside an awesome graphics engine.
Combat is furious, but can be paused at any time for pin-point targeting using the VATS targeting system. This matches the targeting system from the earlier games well, and gives time to pause, think through your next few moves. Also, the VATS system enables some cool, slow-mo action sequences. Otherwise, you can run the game from first-person or 3rd person as you like.
The graphics are awesome, even on my older machine, which runs about middle of the pack as far as computer systems go. The game runs smoothly, but has a tendency to close out after a few hours of playing. I'm not sure if this is a bug with the game or a problem with my computer.
Story wise, it's nothing jaw dropping, but fun and engaging so far. References to other post apocalyptic fiction and prior games abound. The Fallout setting has some unique quirkiness that sets it apart from a generic post-apocalyptic game. Your character is very customizable, and your skill choices actually impact the game--having one skill may make an adventure easier to complete, provide access to an off-limits area, etc.
Still playing it, having a blast--will have more later!