It depends on the guitar. For example on vintage spec Strats the low and high E strings are outside of the polepieces of the bridge pickup, but line up more evenly over the polepieces of the neck pickup.
While on modern style (narrower bridge) Strats the strings line up perfectly over the bridge pickup, but both e strings are inside of the neck pickup poles.
There's nothing I can do about it and the sound isn't affected so I chose 'not care'.
I care, but I'm not obsessive about it. As long as the string passes over the screwhead there should be no problem. (..we are talking humbuckers I assume?). Anyway, the correction is to just give a slight bend to the mounting legs on the baseplate. Tweak it between string changes and it will eventually be perfect.
It depends on how you feel about the guitar. My main guitar is a 94 Ibanez RG that's pretty beat up, I changed the tremolo to a floyd rose and its smaller than the original trem that came on the guitar, so there's a large gap along the top and rear of the trem route. I swapped out the 5 position switch for a toggle so there's an empty blade switch route on the pick guard. If the pickup poles didn't align it wouldn't bother me at all, I own that guitar purely to play. On the other hand I have a Warmoth Strat I put together, one piece Korina body with a quilt maple top finished in light amber, birds eye maple neck, I hardly ever play it but it's just so pretty, if the poles didn't line up on that one it really would bother me, so, horses for courses.
It depends and, for me, has the greatest effect on the top and bottom strings. If you pick a note the toward the outside (downstroke on top string, upstroke on bottom string), it might be quieter because the string is pushed away from the polepiece.