I guess the question is are you asking from a usability perspective or the bees preference?
I think my question relates more to a beekeeper's perspective. It is very difficult to determine what the bees want. I can't imagine the drones telling the workers "Hey, girls, the other hives in this apiary are so much better than this one, you ought to down tools!". The bees will make do with what they have.
If you are talking usability, then it come down to how much weight you are comfortable lifting. Most people prefer less weight, but as you stated, more frames equates to longer inspections.
True, frame weight would be one thing. It would mean that one can't wave the frame about like a smaller frame, and would have to inspect it while holding it diagonally, or by hanging it off a frame holder. The time saved on inspections would be useful to me personally and I won't be working with hundreds of hives, so the weight issue ought to be okay.
But do you mean to say that you would personally not be bothered by the fact that you can't manipulate the brood nest by e.g. switching brood boxes around, or by e.g. adding a super or another brood box inbetween two existing brood boxes, to encourage the bees to increase the brood nest size?
If you are talking about the bee's preference, then it is one large brood nest. I have never seen a feral colony intentionally break up a brood nest.
Yes, although I can't help but wonder whether a "hole" in the middle of the brood nest isn't useful for the queen, to get to more frames quickly, thereby having the possibility to increase the amount of brood quicker (this would be for the beekeeper's benefit).