Looks like you're getting a lot of opinions on this post. Well, as I am currently going through the same decision, I would like to share my thoughts as well.
I am also weighing up the 300 2.8 and 400 f4DO. My experience is that I want hand-holdability and IS capability over other features.. However image quality must be at least "good". Many say that a 300 2.8 + 1.4 is sharper than a 400 DO.. However my experience in using TC's is that they slow the focus and degrade optical performance and lengthen the lens, unbalancing it's proportion and affecting hand-holdability. This is the case with my 70-200, with the 1.4TC and especially with the 2xTC. If you are going from zoom telephotos then the I think the image quality of the 400DO will be better. It is not comparable to it's own breed (Canon IS telephotos) but it should be better than L zooms.. so in actual fact your image quality should improve, compared to the lenses you have been using. This is however a "hunch" so if anyone can comment on this comparison (70-200 and 100-400 vs the 400DO) then this would be helpful.
Also, another suggestion.. generally try to double the focal length of your lenses, especially at the telephoto end. That means if you have a 70-200 then rather go for a 400 in whatever guise (DO, 5.6, 2.8IS) instead of the 300, as the incremental reach of a 300 over a 200 is not really that great.
So, in conclusion, if you can live with the marginal loss of image quality (sharpness and contrast which are both easily corrected in photoshop) then I would suggest the 400DO. The best lens is the one you use the most, have pleasure in using and that gives you the results you need. Simply having the sharpest lens at the expense of portability and convenience is not, I believe, the right approach for all of us. Perhaps the ardent pro who is in competition with other pro's and makes money from his images.. but in that case the pro in question will have a lens for very specific situations, not just one. If you are looking to please yourself and your audience with your images then go for whatever feels most confortable, as that is the lens you will take more often and get more pictures with.
As for me... well, cost is an issue so I have delayed in purchasing either the 300 or 400.. and picked up a Pentax 500 f4.5 screw mount manual focus lens.. A 30 year old lens that is a real pain to work with, but it gives me the reach I need for African wildlife.. and it only cost me $500!
In time I will come around to going for a Canon telephoto.. and by then my experiences might have changed my outlook... but for the moment I suggest the 400 DO.
Hope this helps.