I think a lot of it is mental. There is no reason Roddick should do well at the US Open other than he has the pressure and support to do well.
Pete Sampras never won the French, its a totally different game than the hard courts (US & Australian) and the grass of Wimbledon. Roger Federer faces the same challenge. His game is not as suited for clay whereas Nadal's is. My wife who is a tennis junkie tells me that Roger hasn't played much tennis this year and that is part of his problem. I stopped paying close attention to tennis after Pete retired.
It's been years since I followed tennis (which I was somewhat avid about during a time in the past), but I have randomly got a chance to watch Federer play in some gigantic game in recent history, and his performance was freaking insane... like all-time-greatest-men's-tennis-player-in-history insane.
Well Pete had more of an excuse than Fed does. Pete was pure serve and volley and that game doesn't win out at the French. You have to play great baseline tennis. And Federer is the very best at that.
If it weren't for Nadal, he'd likely have one by now. Unfortunately Nadal is a reality and isn't going anywhere anytime soon. Federer's only hope is for Nadal to be upset early in the tourament because I don't think he can beat him (on clay). Also, with Nadal's aggressive style of play an injury is always possible.
As far as I know, he's only beaten him once on clay (in a Master's Series tournament). That win ended Nadal 81 match streak. I'm not saying it's impossible, but Nadal is clearly the superior player on that surface (just like it's not impossible for Nadal to beat Federer on grass, but come on...). Also, I think things are a little more serious when they play at Roland Garros. IMO another poor sign for any Federer success at the French is the fact that he struggled a little from the baseline in Australia. Typically his footwork is perfect and his angles are so creative. Not so much this year. He forced forced to rely more on his serve (notice the huge number of aces in the 5 set match). If that trend continues he'll be doomed at the French. The clay can neutralize a big serve, and a healthy Nadal will pick him apart if he's not hitting solid ground strokes.