EDIT: @ alpha_dk
Oh, I see. I'm assuming that you're meaning a "low-heart" run when referring to level, ie. you pick up as few heart containers as possible during the game. And while it is perfectly feasible to beat most Zelda games with minimum hearts, it can get pretty damn tough later on, when regular enemies become strong enough to one-shot you. And bosses require additional items to take down almost every time.
And I'd still say that you CAN kill any enemy in Fallout 3 right out of the gate. Since DR caps at 85% (and no enemy has anything near this) and no armor in the game has damage threshold values anymore, you are basically capable of damaging, and eventually killing, every enemy with every weapon.
But that's kind of beside the point.
EDIT2: What mrstickball said.
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