The strings will be imbalanced in volume in your clean signal if you use a non-f-spaced humbucker. Usually you'll notice that the low and high e are a tiny bit less loud than the other strings if you're playing sparkly clean. I don't think I'd say it's a huge problem for a couple reasons:
- If you play with compression, overdrive, or distortion the effect is largely moot . . . and I don't know any guitarists who avoid all three regularly.
- Often you can play with the screw polepiece height to make up for the difference
FWIW - I find the string volume difference between flat pole and staggered pole single coils to be bigger than f-spaced and gibson spaced 'buckers, and most people seem fine with staggered poles . . . so this probably doesn't bother many people.