To score a critical hit on a human, shoot their head. With a sniper rifle this usually kills instantly For a Skag, shoot it in the face when its mouth is open. This varies depending on the type. For the pups, shoot them while they roar at you. For adults, shoot them while they jump at you. For the spitters, shoot their mouths while they fire their poison projectile at you. Critical hits are easiest at close range with a shotgun or scattergun.