With the Moonlander, I do exactly this on my left thumb cluster. I get really easy combos of Shift, Cmd, and/or Option. Ctrl is harder to combine with my thumb,

With the Moonlander, I do exactly this on my left thumb cluster. I get really easy combos of Shift, Cmd, and/or Option. Ctrl is harder to combine with my thumb, so I have alternate modifier keys, too -- left Shift left of Z, left Ctrl by holding down Z, and left Alt by holding down X.