Does hit location matter for damage?
Hit location very much matters. Head shots or in general 'weak' areas will take more damage even when out of VATS. Additionally you can cripple different parts of creatures limiting their ability to attack, disarming them or even crumbling them to the ground. The easiest place to see things of this nature are with Feral Ghouls because they are easy to cripple their appendages lowering their ability to attack you or forcing them to crawl at you.