This is probably one of the most overlooked issue in this topic on hand.
I've got people telling me "Are you crazy???" when I show them my UI: my hotbar having several Alt+hotkeys that people find awkward to use in mid-combat like Alt+Z/X/C/F, etc. But I rarely had issue with this (thank you, 'Piano fingers' lol). At the same time, I'm also amazed when I saw my friend playing on console with their controller. I saw all those hotbar swapping etc and I was like "How did you do that so far?!"
People can probably give general tips like "Don't put your important, frequently used buttons too far away." but ultimately it's up to us to figure out ourselves which setup works the best.