Hit Points.
Anything that models real-world health and sickness and injury better would be a huge step forward for the game. The key is to keep it comprehensible for the average gamer, which is why it's been so hard to do.
I probably woulkd not play it and I suspect that many others would not either.
I spent many years in search of more realistic combat models and what experience, research, life and gaming has taught me about fighting is that it is too dangerous.
It does not make for good heroic fantasy, hit point mechanics make for more predictible mechanics. Now a good argument could be made that 4e could do with a little more swing in the combats.