I use the mouse lefty, and the keyboard with the right. Arrow keys for motion, and a Rosewill RK-9000 mech keyboard, wired for PS2.
USB limits you to 6 key presses per transfer.
PS2 is 'all key presses get sent' 200 times a second in hardware with a decent mobo.
I have every key programmed for something, and I've been using some of the main ones for >30 years now.
I had to learn a new whole set of "fast functions" when Crysis came out; adding cloaking, armor, and all really was hard to do for a bit.
A side effect we noticed after the new functions were working was that when you change the function of a key, it "takes" much faster. Something in the rewiring, I guess.