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Just test it with your right thumb: Imagine you're using a symmetrical gamepad where both thumbsticks are placed on the height of the left stick of the 360-pad. That may be the most comfortable design, BUT... try to press the square/X button to reload in whatever game and (as quickly as possible) return to the right stick.

Now imagine doing the same procedure on a 360-pad: This way you are slightly faster. The left stick's position is the most comfortable, and because the D-pad is not used as often as the stick almost efficiently perfect. The right stick's position is not the most comfortable but gives the upper hand in reaction; switching between the right stick and buttons happens considerably more often so it is efficiently perfect.

Short: The asymmetrical thumbsticks the 360-pad has to offer are the best balance between a comfortable and efficient design -> the most ergonomic design.