The one time I ran out of gas, it was only 4 miles after the last bar started blinking. I've also read of people who only refill the tank when they've consumed 10 gallons of gas since the last fill-up, even if the last bar has been blinking for the last 100 miles. (If you reset the trip mileage when you fill up, you have used 10 gallons of gas when the mileage is 1/10th of the distance, e.g. 48.2 mpg and 482 mi.)
If you run out of gas, you will be able to run in battery-only mode for a few miles (probably less than 5 miles, depending on your battery's state of charge at the time you run out of gas). That might get you to a close gas station, and it probably won't hurt the car, but if you try to go too far, you run the risk of a deep discharge of the (expensive) main battery, which shortens its life span.
The conclusion is that the flexible bladder in the Prius (which is sensitive to temperature and maybe also air pressure) makes it impossible to know exactly how much gas is left in your tank at any particular time. So, there's no point in measuring mileage on a per-tank basis, and there's no point in trying to maximize your miles-traveled-per-tank-of-gas. (It can become a game to try to go a little farther on this tank of gas than last time.)
I recommend filling up whenever you get down to 2 bars, and just work on maximizing your trip mileage for fun.
Douglas (2002 Silver, Wisconsin)