My instinct is that airflow partitioning is less important with vertical airflow cases. If the air flows in a straight line from bottom to top it will tend to segregate itself. If you are trying to force the airflow round corners or against convection it will tend to mix and probably become turbulent. But I would be worried by the outlet side of the airflow in this case - there does not seem to be an outlet above the drive stack and three large inlet fans against one smaller outlet fan seems unbalanced. I'll be interested to see the independent tests.

5.25" modular control panels etc. are less worrying since they are generally quite shallow compared to optical drives. However even one optical drive is a problem in a case like this because it forms such a large obstruction to vertical airflow. I have seen one case that mounts a standard optical drive with the tray extending vertically downward from an overhang. I would be attracted to the idea of one that popped the tray up like a toaster - indeed a case which only used the top surface would be a nice departure. Hot-swap 3.5" HDs could drop in from the top retained by gravity.

I do not think cable length is a significant barrier - extension cables are readily available, particularly for USB.

I hear what you say about the evolution of cases, I have an old Lian-Le full cube about 10 years old which is great but has inadequate cooling by modern standards and is now very battered. I think the vertical motherboard configuration makes so much sense for air cooling that hopefully it will catch on. However I would also like the full-cube layout (with the other components mounted behind the motherboard) to make a comeback - the full-tower is becoming ridiculously deep compared to its width.