It depends what you are shooting, but I finally pulled the trigger on the 400mm f/5.6 a year ago. I already had the 70-200mm f/2.8 IS II, and for BIF I tried the 1.4X and 2X Version III TCs. For general wildlife I still use the the TCs to have IS. The IQ loss with the 2X is modest, but the focus speed by design is drastically slower than the 400mm prime. With the 70-200 & 2X TC combination, if I lost focus on a bird in flight, the focus would get lost on the sky and never recapture it. With the 400mm, particularly set on 8.5m focus limit, the prime can reacquire focus quickly. Even though I have read many comments discounting the auto-focus capability of the 6D, I have been very pleased with the 6D / 400mm f/5.6 combination. I crank the ISO up as needed to keep the shutter speed at 1/1000, shooting everything handheld. The 400mm 6D combo is quite light weight, well balanced and a joy to use. With the newer Canon bodies, I don't find noise an issue, and I don't need to spend a fortune on a big white that too heavy to hand hold for any length of time.