This whole sticks symmetry argument is just a huge ball of confirmation bias in action.
Yeah I think that you can get used to any controller design really. That's not to say that some designs aren't better starting points though.
I guess that the ideal layout is one where both hands are in as similar and as neutral a position as possible. If you were to put your hands into that position in the air in front of you I think you have a good starting point for building a controller around
In terms of stick layout (symmetrical vs asymmetrical), for a game involving dual stick input the most important controls are going to be the two sticks and the two triggers (be they the Xbox triggers or L1/R1 on a DualShock). From an ergonomic point of view I can't see how asymmetrical sticks make sense (in a dual stick input sense) unless symmetrical sticks result in your thumbs banging into each other when both sticks are pushed as far toward the middle of the controller as possible. These days most shooters (both first and third person) rely very heavily on dual stick input.
For a game that relies primarily on one stick input and the face buttons (e.g. third person platformers and slash 'em ups) the asymmetrical stick layout makes much more sense. Personally though, I tend not to rest my thumb in the middle of the face buttons, but rather on the bottom one, so the difference between the way I hold my two hands is fairly minimal (given that the lower face button is only barely above the left stick in a symmetrical stick layout controller like the DS3).
So I guess any controller is going to be a compromise between those two competing interests. Personally, I play a lot more FPS and TPS games, for much longer periods of time, and so dual stick input games are the ones that concern em the most in terms of a controller. I think that dual stick control input really does require much finer grained and constant control as well, whereas face buttons (especially digital face buttons) require only fairly simple input.
All that being said though I can understand why somebody would not want to change from a layout they've gotten used to. It would be nice if the console manufacturers opened things up to third parties a bit more so that people can find a controller they prefer. Things like the trackpad probably complicate that a lot, but we can dream...