U.S. major airlines and big airplanes are about 10X safer than cars on average. (But, of course, planes go 10X faster, so per unit of time, they are about the same). Counting driving to Logan, flying into NYC, and risking my life with Osama the taxi driver from the airport into Manhattan, I'd rather drive. Elapsed time is only a little better by air.
Commuter airlines suck, according to the statistics - they are no safer than driving the same distance, but I don't know by how much air taxis in Alaska and other high-risk categories throw off the number.
So buy a big fat body-on-frame SUV, don't drive when sleepy, and I think you may be at least as safe as flying.
The first few minutes and last few minutes of any flight are the most dangerous. Generally, once a plane has reached cruising altitude the risk of something catastrophic happening before landing isn't affected much by the distance traveled. The risks of airplane travel may generally be best assessed as risk per flight.
In a car, however, the risk per mile is roughly the same on long trips and short trips. The risks of auto travel are thus best measured as risk per mile.
For short trips, the risk of a fatal crash when driving is probably no worse than when flying. For long trips, though, the risks of a crash happening at some time during the trip increas. By contrast, the risk of a crash on an airplane is independent of trip length, so for long trips planes are safer than cars.