Well, I did hear he's reinstating Damage Thresholds, so I don't think any newbie with a 10mm pistol will be killing a random patrol of Power Armored Outcasts anytime soon.
On the other hand, that would mean that at high levels you could be even more overpowered, in Fallout 3, by the time you have power armor, plasma weapons, and are level twenty, raiders with 10mm pistols could still kill you, you'd have to be acting really stupid for it to happen, but you wouldn't be completely impervious to their attacks. If damage thresholds did return, I could see the player becoming completely invulnerable to most enemies. Of course, from a logic standpoint, when you have power armor, it is sort of reasonable that weaker enemies wouldn't stand a chance against you, but if there aren't enough high level enemies to go around, the game could become very easy at that point.
But yes, I hope Obsidian can balance the game better, Bethesda's games always seem to be purely balanced, but maybe in the hands of another developer, New Vegas will turn out a little better in this regard.