As the owner of all 3 calibers, I would not be afraid to use any of them in a defensive situation. Like some of the others have said it is just a matter of personal preference. I carry my M&P 40c for everyday business (I know "Tupperware" or "Plastic Fantastic" gun) but I like it and it fits well as a CC gun. I do carry my 686 6" when I am in the woods, gives me a little more range. Now for my 645, well that is just a Fun Gun to shoot! I reload for all of them so running 100's of rounds through them an a regular basis is not a $$$ Issue. (Use Factory Ammo for Carry Though)
Just to add a little more to this topic here is another link I found.
Suggested Calibers & Loads
The three calibers are, In my mind Very Equal!