Protesilaos (Prot) has an excellent post on keyboard ergonomics for Emacs users. He considers various strategies for making Emacs commands easier to use and less likely to cause RSI damage. He considers everything from split keyboards to evil-mode.
He says he has both a split keyboard and a keyboard with a normal form factor. He says that the split keyboard is not a magic solution and that what works best for him is to configure “one shot modifiers” where the modifier is simply pressed—but not held down—before the key it modifies. So, to use his example, Ctrl+x is typed by tapping the Ctrl key and then the x key.
Along with that he suggests ordering the modifier keys in a way you find comfortable. The most important thing, he says, is to keep the Ctrl key close to the space bar so that you can use your thumb to press it. It’s also important to have the modifier keys located symmetrically so that, for example, you can use either hand for the Ctrl key.
As for the common advice to map Caps Lock to Ctrl, Prot says that’s okay but that it encourages the bad habit of always using your left pinky for Ctrl.
There’s a lot more information in Prot’s post—including how to configure one shot modifiers—so be sure to take a look at it.
I’ve been incredibly lucky. I use a standard keyboard, map Caps Lock to Ctrl and don’t have any symmetric modifier keys. Nonetheless, I haven’t suffered any RSI problems despite spending the majority of my day at the keyboard. But, as I say, I’m lucky. The smart thing to do is to read and head Prot’s advice.