No difference between the two except that 16/2 only has two conductors which is enough for one speaker and 16/4 has four conductors which can accomodate a pair of speakers.
It's common to run 16/4 from the amp to the keypad/volume control location and then 16/2 branched off from this location out to the speakers.
16ga wiring will be good for whole-house audio applications out to about 100ft. If you have runs that are longer, it would be best to step up to 14ga speaker wire.
Cheers,
Paul