Regarding the layout: This thing is intended primarily for playing games for which the D-pad is the primary input, not the analog stick. It makes sense for the D-pad to be in the primary position in that case. The criticism against the Dual Shock is that with the move to 3D games, the analog stick should have been moved to the primary position. Also, judging by the width of the cord, D-pad, and buttons, this thing's pretty small. I doubt it will be as much of a reach to the analog sticks on this controller as it is on the Dual Shock.
For N64 games, I hope that the controls can be customized. for games that just use the C buttons for camera control, the stick would work fine, but for some games it would be nice to be able to choose which buttons do what. With the extra shoulder buttons, every button could be remapped, although the best layout for each game might be different.
I'm not convinced this is the final design. The home button isn't recessed like it is on the new remote, for starters, and it's not wireless.