On a normal, staggered keyboard, I hit space with my right thumb, and alternate shift, unless I'm typing a word in allcaps, then I just hold shift down with my left pinky; I swap the capslock key for control.
For the last several weeks, I've been trying to alternate shifts with my thumbs, on an ErgoDox. Today, I finally gave up on that experiment, because I found my thumbs confusing the shift keys with space and backspace (right thumb gets space and enter; left thumb gets backspace, delete, and control). It was happening enough that it was annoying me. Now, I need to get used to having shift on my pinkies again.
And for an additional datapoint, on a TECK, I have space on my right thumb, backspace on my left thumb, enter usually on my right thumb. I alternate shift with my pinkies, and only hit control with my left pinky.