LogFAQs > #984539227

Optimally, the parts of the controller that get used the most often should be lined up with the most neutral position for the thumbs, which is generally the upper two quadrants. The problem is that different types of games focus on different parts of the controller, so there isn't really a blanket "this is best" claim that can be made. The WiiU's configuration of having both sticks in the upper quadrants is better for shooters and other games where you'll be using the right stick more than the face buttons, but worse for games that make extensive use of the d-pad and/or face buttons.

To try and make a blanket statement, I would say that most games worst best with an asymmetrical layout, but that's a suggestion that should be taken with several grains of salt because it'll depend on what sorts of games an individual likes to play.