My feeling is that we probably don't want to rotate either of the half slots, as that would cause more inconsistency in the project template (and I don't think it is necessary to make the CoBs routable).
I think the non-power pins in the default templates should be harmonized so that by default there are the same number of pins of each type, in the same order, starting from the same spot. For the quarter slot I'd reduce the number of biderectional to 32 but keep everything else the same (2 analog + 12 inputs).
Obviously you expect people to customise the pins, but if there was a clearly documented pinout of the 70-pin connector that matched the default template, and the template was consistent across the slots, it should reduce confusion.
It would be good to fix things so that the die didn't need to be rotated. I suspect changing the project template to move power pin locations would be unpopular at this point, so my feeling is the best fix would be to change the CoB pinout. That would obviously mean if a project was on both run 1 and run 2 it would need a motherboard respin. Unless maybe the mezzanine pinout could stay the same except rotated 180 degrees, then you could just plug the run 2 CoBs in rotated 180 degrees compared to run 1 CoBs?