If you look at the sample controller mapping, you might note that all the abxy buttons are mapped to communication functions, so I'd say they aren't intended to be natural to get to (much like the start button on other gamepads).
The ergonomic buttons like the triggers and rear buttons are best for actions you need to perform while moving. There's six of those in total. Compare to WASD and a common 3-button mouse setup: the mouse buttons, shift/ctrl, and the easy-to-reach keys 1234EQZXCF. So yeah, you won't have as many quick-reach keys available to you. I would grade the keyboard keys as a bit harder to reach though because you have to take fingers off movement to hit them.
The ergonomic buttons like the triggers and rear buttons are best for actions you need to perform while moving. There's six of those in total. Compare to WASD and a common 3-button mouse setup: the mouse buttons, shift/ctrl, and the easy-to-reach keys 1234EQZXCF. So yeah, you won't have as many quick-reach keys available to you. I would grade the keyboard keys as a bit harder to reach though because you have to take fingers off movement to hit them.