Hi Jon,
These are all point of ease of use really.
Now I see the whole picture, you have addressed quite a few limitations on standard design for rigidity, etc. But there is always a compromise on access and travel distances. I can also see there is room for linier gauges if you want them later.

Because of the limit or gap between the bed and under the gantry, I am assuming that the Z axis travel to the bed is 200mm for my example, 2nd picture shows the tool down. Now looking at the first picture, tool up, the travel is only going to be as high as the Z ball screw length. So my suggestion is to double the bed to gantry gap size and use that as the ball screw length (400mm). This will allow you to use long tools that need to machine through the 200mm. So the Z ball screw needs to be 400mm to cater for the machine dimensions.

One other point on the use of the machine, being as you will have to work over the Y axis rails for job setting it could be quite difficult to set a job “inside this area”. Also as the machine has sides if you have a larger piece of work there needs to be an opportunity to hang the work over the edge. The X axis should be ok for long jobs and you have given enough to push the work through the X axis and machine the next section providing you leave the gap at the back. I have just recently machined a kitchen cooker hob aperture in a very long worktop, much bigger that the machine length. The Y is always a restriction so I made sure I could cope with at least 700mm so I can cut outside the standard 600mm units on the machine Y length. Your design seems to handle all this ok.

The last picture “Side View” shows the elevation on the bearing widths quite well; there you can see the spindle in line with the front Y bearing, this is where you could increase the end piece length to move that bearing to the same distance as the one at the back from the spindle centre and give yourself a equal pressure on these bearing in the Z axis when tool pressure is applied. I know that will reduce the Y axis working distance. You have said that this point was already on you to do list and now done. :-)

How are you going to set, adjust and maintain the X, Y and Z squareness?
The nice thing about two Y axis ball screws is you could independently adjust to fine tune the X and Y squareness. The Y Z plane can be adjusted ok using the fixing into the end pieces but need to consider how to adjust the X Z plane as this will be dependent on the construction. It may be worth thinking about this because when finished getting it all square can be a nightmare of rebuilding with shims, etc. This of course depends how accurate you want is all to be. Of course you could bolt it all together and it may come out spot on for you, in my experience a Gantry Mill is always out of square and needs some mechanism for fine adjustment.

Other minor points
Another spindle (Motor) brace at the top of the motor
Axis stepper cable management particularly for the X behind the gantry

It is looking good, nice CAD what do you use?
Regards