I tried Dvorak for a month a few years ago. For me it was just useless agony, not only with key positions but also with app/OS shortcuts that are very much designed for qwerty layout.
I have since switched to a split ergonomic keyboard (Diverge 3) and adjusted the layout somewhat (kept qwerty, but put all the modifier keys in custom locations). That took me about a month to exceed my previous speed. Typing on standard keyboards when needed is not a problem either.
It would be interesting to design a keyboard whose key arrangement is weighted toward standard shortcut combinations. Maybe put them mostly on the left hand side to allow (right-handed) mousing without looking at the keyboard.
Keyboards like Diverge and Ergodox are fully programmable so nothing's stopping you from doing that today!
Also, I found that putting a small touchpad^ in a thumb-accessible area (near where a laptop touchpad would be) is a good enough replacement for a mouse.
Well yeah, but what about the rest of the keys? It's one thing to put all the shortcut keys on the left or right side, but quite another to arrange the keys so that typing is...possible.
You don't have to change from the qwerty layout for general typing.
For example, you can program the keyboard in such a way that pressing X+A sends Ctrl+C keys to the OS, where X is a custom modifier button (Not Ctrl but a separate button that you assign for this use case) and A is, well, whatever other button on the keyboard you want to use for this, not necessarily "C".
Or you can have a single button programmed to send Alt+Tab, or... whatever, really, the firmware is very flexible.
Yeah, I know about remapping and that's not going to happen. What a nightmare! But the more I think about my idea the worse it sounds. What are the 12 most common shortcut keys? It's hard to narrow them down to that, and I'm not sure everybody would agree. Still, ergonomically it would be an interesting challenge.
I have since switched to a split ergonomic keyboard (Diverge 3) and adjusted the layout somewhat (kept qwerty, but put all the modifier keys in custom locations). That took me about a month to exceed my previous speed. Typing on standard keyboards when needed is not a problem either.
I never cared to measure my typing speed though.