The 300 f/2.8 with TCs is much sharper than the 100-400mm. If you are going on a bird shoot on Safari, then I would definitely prefer the prime. But, my experience from my one safari is that the zoom would be far more useful for the wild life as the game wardens take you very close to the big game and the 300 would be useless. (I have both sets of lens and would pack the 100-400, which retracts nicely to a small size too).
Alan good points. I have been to Sabi sands in Kruger before where we could off road and come real close to game. However this time I will be in main Masai Mara reserve and we are not permitted to off road. Game could be far or close depending upon luck but if far we would not be able to drive to them.