You're absolutely right, DirtyD. In the 'standard' button layout, with button 1, 2 and 3 on the top row, you are constantly reaching over button 4, 5 and 6 in most games. I think it's just a natural tendancy to arrange things in that way, the same way we read print (in Western countries) - left to right, top to bottom. Furthermore, as we can all recall from the days when we used to play MAME on our computer keyboards, the layout was exactly as you are describing it - button 1, 2 and 3 on the bottom row (Ctrl, Alt and Space), and 4, 5 and 6 above.
So go for it man, set it up the way it makes sense to you. I can't even say that you are causing yourself much extra work with the need to re-map game imputs, because if I recall, the default MAME button mappings for most 5- and 6- button games don't line up with the 'standard' 6-button layout anyway.
-EVEGames