"DeusEx"

[Jonathan]

Are there any thoughts about using 6 bearings instead of 4 on an axis, specifically here I'm thinking of 25mm supported rail?

You will reduce the contact force on each bearing. It's worth remembering that they're rated for a huge force anyway, so it may not be worthwhile. There may be other effects, such as helping with racking - not sure.

...Which also leads me to wonder if there is anywhere to avoid or prefer with the placement of the ballnuts? Centre of mass or axis of the spindle seem to be the most logical? Does that sound reasonable?

The Y-axis ballnut should be as close as you get it to between the rails and not far from the spindle. That ensures that the only thing which can flex, when you apply a force parallel to the Y-axis, is the aluminum. If the ballnut is far away then the bearings can move on the rails relatively easily, leading to quite a bit of deflection.
This is a problem on my machine at the moment:



I think aligning the X-axis ballnuts with the center of mass in the XZ plane (or at least in Z) is a good plan as when the X-axis accelerates you've eliminated the turning moment about the ballnut. Ideally you would do the same for aligning the X-axis ballnut with the Z location of the cutting force, but that clearly moves so the best you can do is an average.

I'm trying to have the bottom of the Y axis about 150mm above the work surface, with 2/3rds of the spindle mounting plate supported on the Y axis when the spindle is at the lowest point of travel... is this something worth the effort?

Yes, do it - the further apart the bearing blocks are placed on any axis the stronger it will be, up to a point.