Played both, and they're such different sports, that I'm not sure they're comparable. Different attributes are considered positives when playing each sport.
As far as conditioning goes, I'll say that soccer demands much more cardio and endurance than American football. On the other hand, I'd say that body strength and muscular physique is much more needed in American football than soccer. Plus, I know there are different positions in soccer, but there are in American football too, and the positions in American football, in my opinion, differ so much more greatly than in soccer.
In soccer, all players must be lean, fast, good foot-eye coordination, and have great endurance.
Offensive and Defensive Lineman - big, a little weight in the middle sometimes helps as they're harder to move. Massive upper body strength. Great footwork and hand speed. Not too fast on their feet. Outside OL and DL, less weight and more muscle. Usually faster and quicker too.
Quarterback - must be able to throw football accurately. Lean, muscular, quick, not always real fast though.
Running Backs (offense) & Linebackers (defense) - huge strength in arms and legs. Must be very, very quick and fast.
Wide Receivers (offense) & Defensive Backs/Safeties (defense) - fastest players on the field. Tall, lean, very, very quick, stop and go speed a huge must.
Tight Ends (offense) - mix between a lineman and wide receiver. Big, muscular, not the fastest, must be able to block and catch passes.
Punters and kickers - specialty skill. Usually not very fast. Usually not the fastest or quickest either.
So all in all, soccer players much better conditioned, American football players, much more muscular. Although depending on position in American Football, many are well conditioned too. Both sports require lots of skill to be good at too. Much more so for certain positions in American football.
Both sports are fun to play and watch. As for a "main" sport in the U.S., there isn't one. Big three are baseball, basketball, and American football. As far as television ratings and attendance, American football would be the most popular.
I know it was kinda a "long winded" answer, but American Football is very different and there's a lot to cover, especially if you're not terribly familiar with it. Also there's a lot of money made in advertising in sports over here, with commercials and stuff. Since soccer doesn't really have timeouts and is continuously played from minute to minute, a lot of companies are reluctant to advertise during soccer games as they can't show a lot of commercials and stuff. Kinda shallow, but in today's America with the sports, everyone's looking to make money off of it, and that includes the companies that advertise commercials during timeouts or whatever when the game's on tv. Oh well!