Let's say 10,000 miles a year, 30 MPG for small car and 15 MPG for large car, and $3/gallon gas. That give an extra $1000 in gas per year for the large car, or an extra $83 per month if a large car is needed once a month, or $28/hour saved for the inconvenience of the hours spent picking up and dropping off the rental.

Either way, the delta is much smaller than what I was expecting, in the range of a couple of hundred a month at the high end, depending on which way the numbers swing. It can be something that's not worth worrying about, for someone who has a middle class income.