It depends on the application, and what forces are affecting it.

Something like a cast iron milling machine with two linear rails, leadscrew position isn't going to make much difference, provided everything is mounted solidly.

Where as something like a flimsy aluminium framed router with unsupported rails, leadscrew position could have a major effect.
You ideally want the lead screw to be acting as directly as possible against typical cutting forces, however that isn't always practical.