I am a lefty, and for vast majority of games it is no issue. The only time I have problems is when DS/3DS expect you to use a stylus and move your character (d-pad or stick are on the left) since I use my left for both.
I have trained myself to use right as could not afford left handed baseball glove and anywhere I worked with computer mouse had to use right.
On a controller both hands are used so no issue. Never really thought about it.








