Having used the 5Dmk3 for about a week now I have to agree with KR that the AF system is the area that I have to get used to most.
I've owned the 300D, 20D and the 1Dmk3 (used it for the last 4.5 years). I'm used to toggle between AF 'modes' (spot AF and 'auto-AF' (where the camera will pick the focus points, choosing from all available points)) just by using the little joystick on the back. Press once: go to the center point. Press twice: switch to the 'auto-AF' mode.
With the 5Dmk3 this is not longer possible to do (as far as I could figure out). First you have to press the AF button, then use the M-Fn button to toggle between the AF modes. You can disable modes that you don't want, but you still have to use another button than the joystick to switch between the AF modes. Hopefully they will fix this with a firmware update, because it's just silly to add extra steps in the selection of the AF modes.
Another thing that quite annoys me is that the focus point is black in the viewfinder. If you're shooting in a dark place it's impossible to see what AF-point you're using. Hopefully they can fix this as well with a firmware update, because now at times you're wondering why the damn thing isn't getting focus, finding out that the focus point is at another place as you're thinking. I prefer the red AF-point in the viewfinder of my 1Dmk3.
Other than that: I love the camera
And I will even be more in love when the battery grip will finally arrive!