From my own experience, it relies mostly on temps. Once you are able to take temps out of the equation (after-market cooling, water loop, whatever), then voltage can become a part of the mix.
With the new gens of cards, this may be different. The new chips don't run as hot as the old chips do. Since heat may not be as big of a factor, voltage could step onto the scene a bit earlier.
I would do some serious research into it before I pumped extra volage through a $500+ card. I am sure there are several yahoos out there in cyberland who have tested the limits, exceeded the limits, and have the blackened chunks of silicon to prove it. Surely some of these have posted up their stupidity for others to learn from.