Most clipless systems come with some degree of float. So you can tailor it to your liking by playing with that. Also, a good fitter will be able to use cleat wedges to both angle the shoe and raise the shoe to take foot pronation, knee tracking and leg length discrepancies into account. Having said all that, your body is fairly remarkable at adapting to less than ideal positions. I recall watching a recent video of Emma Pooley getting a bike fit on the GCN channel. The fitter discovered that she has a leg length discrepancy of about 4mm. She rode professonally with that for years without knowing about it before she joined GCN. She won the TT world champs in the past, so I would assume that she wasn't "affected" that much by the less than ideal position.

Edit: Found the video.