Why does unequal amounts of RAM in each slot decrease performance?

With equal amounts of memory in both slots, memory can be "interleaved" so that successive chunks of memory alternate slots. That way, memory accesses get distributed to both slots almost perfectly evenly, allowing their bandwidth to combine. With uneven amounts, memory cannot be interleaved and has to be mapped first to one stick and then to the other. A program that is accessing a large contiguous chunk of memory will find almost all of its accesses going to one stick, and there will be no bandwidth combination.

Additional Notes: For best performance, fill both memory slots, installing an equal memory module in each slot.

The likely technical explanation here is that your MacBook(motherboard) supports dual- channel architecture, and thus requires 2 identical memory modules. Benchmarks suggests that it gives 5%-10% performance boost.

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)?

When two non-identical memory modules are used, the motherboard will run the memory modules at the speed of slowest module.