How do you make your Dualshock controller more comfortable for XIV?

[Erys]

It's the first. Though I did have hand therapy, I am nervous to rearrange my hotbar. Is it really more optimal to change it?

Depends on how you rearrange it. My example, I have combo skills (actions you are going to be pressing a lot) on the dpad, which wouldn't allow to move and attack at the same time (dpad and movement being on the same hand) unless you assume weird hand positions.

Ideally in your case you'd want to deviate from putting any skills on dpad keys and just go full triangle/square/x/circle. That way your left hand will only have to focus on trigger and joystick, getting rid of the dpad. It's the only real concession you can make when rearranging stuff on a controller, getting rid of finger gymnastics as much as you can.

Another thing that helps is rearranging your combos in ways that don't force you to react. For example making a 3 steps combo R2+square triangle circle so it follows a semicircular pattern clockwise pattern so you don't "panic" searching for the next skill, deeply rooting it in your muscle memory, further reducing gymnastics and sudden movements that could strain your hands. And practicing, a few minutes of practice a day will help your muscles to build some resistance and memory, just don't overdo things.

Keyboard and mouse not an option? Much more relaxed and much easier to operate for this type of game.

This depends on the person, I have a hard time with keyboard and mouse since they lack a certain feedback that the controller gives me. And the position on hands and arms is really awkward, doesn't really hurt but yeah.
He could try but it's not for everybody.