In every U.S. jurisdiction I'm aware of, you can use the level of force that is reasonably necessary to effect self-defense or defense of another. So it depends on what sort of assault we're talking about. If the assault involves a deadly weapon, or multiple attackers and a defenseless victim who is still being assaulted despite already being prone, deadly force would likely be legal. If, for example, the assailants are unarmed and kicking a prone victim in the head repeatedly, the threat of deadly force might be the reasonable course, followed by the application of force if the threat does not stop the attack. But even then, how do you know whether someone is unarmed? It is always a factual determination based on the particular circumstances, and the standard is reasonableness.
In addition, some states evaluate reasonableness subjectively ("reasonable to me based on my subjective perception of the circumstances"), while others (most, I think) use an objective test (the hypothetical "reasonable person"). I realize that what I've called an objective test might seem subjective as well, but that's the legal jargon. Also, some states require that in self-defense situations you must retreat if you can safely do so. Some states have a duty to retreat except in one's home. Some states have no duty to retreat.