On the June issue of Game Informer there’s a one page interview with Todd Howard about Fallout 3, here’s a small transcript from NMA:
Has it been difficult to find a balance between open aiming and the tactical V.A.T.S. system? Will it be possible to play the game without tapping into V.A.T.S.?
We’ve been tweaking it, but it’s been going pretty smoothly. You can play the game without ever using V.A.T.S., but you’ll miss some of the more fun moments. We have people who play the game here and some use V.A.T.S. exclusively and some never use it. My hope is that the average player will use it about 50 percent of the time. The two modes are meant to complement each other.
Outside of Megaton, what’s an example of how the game might be different upon replay
Without spoiling anything, I can say that the game changes pretty dramatically based on two main things: whether you are good or evil, and the skills you choose. It makes for very different experiences.
More info on NeoGaf.