This page describes the RAM specifications for many of the MacBook laptops. In the section for my laptop (13" Pro Late 2011), it says:
Additional Notes: For best performance, fill both memory slots, installing an equal memory module in each slot.
This isn't the first time I've heard of this phenomenon, and it's definitely not specific to Apple.
Why is this the case? Other than the obvious decrease in available memory, why would it be worse to run with 6GB (1x4GB + 1x2GB) than with 8GB (2x4GB)?