I haven’t read through all the many back posts that debate size constraints, but from what I have read and what I experience, having a larger build for MPCNC has issues. I am able to do 32" x 32" but I haven’t pushed into harder woods or aluminum. One thing as you note is that a bigger build means the jobs will be lots longer since you would be generally using smaller tooling and low feed rates in comparison to more robust builds with larger stepper and perhaps with rack and pinion axes.
I put in midspan supports but then that makes it a challenge to put in larger pieces of material since the sides are then blocked. Also bigger builds will sag in the middle at the tool mount.
Have you thought about the Low Rider? I have been reading up on it and it seems like the thing to do for bigger builds.