How is the ear fatigue with these?

If you mean comfort wise the clamping force is almost unnoticeable and the pads don't get too hot, so you only have to swivel the cups so your ears don't touch the plastic grill. Sound wise I haven't really noticed any fatigue even after listening for a longer period of time. The sound is pretty balanced and unobtrusive in a way, however when I first got them some higher frequencies sounded a bit harsh but that's because I was used to the Pro 80s sound signature which was more mellow. Both of those things changed after burn-in and getting used to the sound sig. 

"since the CALs aren't really in the same ballpark in terms of sound quality", do you think they're better or worse?
Are the earcups on the MH463 bigger than the Pro 80, or almost the same size?

The CALs are worse in overall sound clarity, instrument separation and soundstage, but they do have nice lows with good bass extension and decent sub-bass as well. They also have a warmer sound signature like the Pro 80s. 
The earcups are the same size fit wise, but the MH463 pads have a bigger opening. I swapped them for the Pro 80s pads but they changed the sound a bit so I'd recommend getting bigger pads in terms of how large the cut where your ears fit is. Something like the Brainwavz hm5 pads would probably fit that bill.