Reducing used samplers is always important. Sampling from 4 textures will require hitting the memory twice as many times as only sampling from 2 textures.
If you’re using techniques which require textures to be sampled multiple times per fragment (parallax offset mapping, texture bombing) or you are performing layered blending, the number of texture samples will increase a lot if you use unpacked.
The advantage of unpacked are if you need to mix and match, like you mentioned, and compression quality (since packed channels may interfer with one another during compression).