Hi JR - I have analysed many gantry and machine configs and each has + and -'s... One thing that can be done is to not have the top rail on the gantry face but move it to the top and back of it. This achieves two things 1) It makes the force on the rails smaller as their distance is further apart so the local deflection is less 2) It makes the centre of action of the moment closer to the shear center of the beam which means it reduces the lozenging of the section. But this then means the saddle is L shaped but my modelling shows its a bit stiffer. This also gives the opportunity of putting the drive on top of the gantry vs on the front if this is of use.... so many combinations.
https://en.wiktionary.org/wiki/shear_centre
https://www.quora.com/What-is-Shear-center
bambachs thesis is a must for any engineer in this field.
To extend your logic on the column config a rising Z bridge solves some problems. Effectively its a double column machine. I intend to do this next machine...
Cheers Peter