I consider a number of factors in determining whether to drive or fly. The most important issue is door-to-door time for flying versus driving versus other reasonable modes of transportation available (e.g., reliable train service). As a rule of thumb the breakeven point is around 4 hours, though for some trips I've estimated that even a short, 60 minute flight would result in a door to door time of 5 hours based on the distance from the nearest airport to my destination.

After door-to-door time I consider schedule convenience, my need for flexibility (when driving I can leave anytime I want without change fees or the uncertainty of standby), whether I need or even want a car at my destination, whether the trip involves very early or late hours when I might be too sleepy to drive safely, weather impact, and the overall costs. An interesting view of overall cost is that if I'm traveling a short flight route with a colleague, driving a rental car is usually cheaper than buying two tickets even if dropoff fees are involved.