16GB DDR4 configuration query

It depends, if you have a quad-channel memory controller like on a LGA-2011 V3 processor, then 4x4 will perform better. If you have a dual-channel memory controller like one on a consumer Skylake platform LGA-1151 processor then it doesn't matter and you're better off with 2x8 for upgradability and the fact that you can generally clock RAM higher if you're only using 2 slots.