Whichever mouse you use, I have found bigger is better. I like the mouse to be large enough for my hand to rest on it without touching the mouse mat. Unfortunately, last time I tried to buy a new mouse I found this was getting hard to do. They keep making mice smaller and I can't find the big ones anymore. Smaller mice make my hand feel cramped and my wrist ache.
I think you have made a good point. I also find small mice require me to hold my hand elevated over it and it must become a strain. I still use my very old Microsoft PS/2 compatible intellimouse. I even sometimes think about putting some padding on the back of it under my palm but I don't want to make it uncomfortable with a bodgy job.
This is what I find with the normal optical mouse, fatigue in the arm using it as opposed to a Trackman (not Trackball) where the ball of your hand is placed firmly on the bench, supporting the weight of your arm and fingers gently wrap around a Trackman, more to locate your hand in the correct position to use it. Then the thumb, forefinger and index finger all rest in their positions; trackball, left and right click buttons. The forefinger only shifts to use the scroll wheel.
I think there are other variables that come into play with RSI and mouse usage, namely seating height and screen size/resolution where if you have to get up close to see the screen then you end up all crunched up instead of being relaxed. I type this with a 24" display 1 meter from my seated position in front of a 800mm high bench.