Flying across the country isn't the chore it was back in the day, but there's still a bit of stress associated with long flights. Sure the chartered flights the NFL teams use are designed with a larger athlete in mind, but some of these flights are still quite lengthy. A comfy chair and a fabulously prepared in-flight meal are nice, but a 5 hour (or longer) flight still can take a toll on even the most physically fit body.
A few years ago Grantland took at look at the winning percentages of teams that had traveled more than 2,000 miles for a game, and from 1997-2011 they only won 39.