There's a stress factor, but a commute doesn't have to be THAT bad. Two hour flight time max, with multiple non-stops on multiple airlines is largely a no-brainer. But if it's a congested hub-to-hub route, and/or populated by senior people it can get hard.

You obviously need enough seniority to bid commutable trips. That varies by airline (at mine the threshold is the junior lineholder).

When I commuted, I would depart about three hours prior to show, which would give me one backup flight (down to the last minute). Holidays might necessitate spending a half or whole day commuting (or just buy a ticket if you don't want to deal with it).

If you draw a two-hour circle around all the major hubs, that vastly opens up your lifestyle options... mountains, rural, mayberry, etc. I wouldn't live in a big city just to avoid a commute. For example, with the time on the road, if you can live near family that can be a HUGE enabler for the spouse who has to cover down when you're gone.