(macOS, the situation is different because it’s ⌘ you’re mostly aiming for rather than Ctrl, and it’s further in which makes it easily thumbable. On other platforms, Super/Fn/Alt/Ctrl might be a decent order, but I think you’d still probably end up wanting Fn to be second in rather than edge. But really, all I actually want is for Fn to be a regular modifier, please, not handled in the firmware where it only works on a few keys and is just dead on the rest. Fn keys are really stupid in this way.)
But yes, Framework firmware FTW.
Of course on other people's laptops I get used to it... But I'd rather have it in the corner!
If you're not talking about tmux - also consider remapping if possible.
Control-space is mark in emacs (even though I am using vscodium these days - I do fire up mg for quick things). It does make it a two handed chord (left control) but it's quite fluid for me.