(5) BackSpace is a good candidate for a single button (especially early on when the wrong character comes out a lot), but it needs to be in the right spot. I'd recommend using a more tailored mapping, e.g. backspice or one you've created for yourself with Twidlit. Training takes a while, better not to waste time on an inferior mapping.
(3) You can certainly use two hands at once, but not to split modifiers from their keys.
I don't find hand positioning an issue these days, except sometimes towards the end of the day on some awkward chords when my muscles get weak.
Perhaps my hands are a good fit, though, and I use a mapping that does not require the thumb buttons.