[Hellstrom]

I think at least part of the answer is that there are random NPCs and then there are not-random NPCs. They may appear the same, but if you get a quest to obtain an item, assassinate a person, etc, the NPC the system creates will be a scaled encounter and can be much MUCH tougher than random civilians. My assassin character has done well over 100 NPC kills, some were easy and some were very, very tough. Like other encounters, the NPCs get random buffs put on them, things like DR and haste. I've seen NPCs with DR up to 15 or so. That made it pretty nasty when my character could do a max of 17 damage in a single blow... i.e. there's a very good reason why "using your wits may be preferable" for those retrieve an item tasks.