IRS mileage rate for 2013 is 56.5 cents per mile, so 500 miles would be $282.50.
Subtract the cost of gas (US new car average of 24.9 mpg, so 20.08 gallons @ $3.269 US average = $65.64) and you're left with $216.86 as the cost of operating a car for a 500 mile trip.
The IRS rates are high, you say. This calculator says between $0.15 - $0.30 per mile for wear and tear. Let's use the low figure, $0.15, which gives us 500 x $0.15 = $75.
Note that "wear and tear" includes depreciation, because the more miles you drive, the lower the car is worth. A 2002 car with 20,000 miles is worth more than the same car with 200,000 miles. It also includes tires, brakes, oil, timing belts, etc because the more you drive, the more often you have to change these things.
Many people don't count those as per-mile costs, and instead act like a new clutch or timing belt is a total surprise, instead of an expected result after so many miles of driving. However, they are valid per-mile costs, and if you budget appropriately, you likely won't ever have $1,000 surprise repairs - you'll just have expected repairs.
So if it costs the rental car company $75 and they charge you $50, how do they make money? Well, it doesn't cost *them* $75.. they have their own mechanics to do oil changes, brakes, tires, etc, and they get bulk rates on parts and fluids.