I don't see any reason why your Z axis plans couldn't be superior for the reasons you stated. Overhanging loads do tend to wear the slides in a particular fashion. The lateral force on the screw is not a major concern, if the slideways are all nice and tight, and long enough to prevent slip-stick locking. If you had the vertical room for it, you could still center your screw drive above the router head, could you not?
Can you make the spindle easily accessible for the tool changes? That would be my primary concern.
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