Taken as a whole, these guys would have to serve really well and hit big throughout a match to win, something that's difficult to do over a best of 5 sets format. That's the "beauty" of ND's, AM's, and RN's games -- THEY don't need to have an "on" day necessarily, i.e., serve really well or hit the ball deep consistently; they can simply play the odds that the opponent can't continue hitting big and serving big the entire match.
Individually, all of these guys have huge holes in their games.
Tsonga -- average lateral movement during a long match, average BH, really poor return of serve. Unless he serves 70+ percent on a fast surface, he is at a disadvantage against one of AM/ND/RN because they can return his serve, he returns theirs poorly, and loses a lot of the rallies. Any service game where he misses a lot of 1st serves and he's doomed. Incidentally, he served really, really well against Federer at Wimbledon, but Federer, despite anecdotal, visceral images of that match, returned his serve well enough. Tsonga won "only" 72% of his first serve points, a number that's not really good for any surface other than clay and is nothing to write home about for grass. I think if he ever got into better shape, he would be able to get to more FHs and hit more of them. I don't know if his return can ever be improved.
Isner -- honestly, Isner's serve isn't as dominant as it seems to be. Karlovic's serve at Karlovic's prime was/is much, much better and more difficult to return. In just about every match against decent or good returners, Isner gets into trouble on a lot of his service games. His return of serve is atrocious, his BH poor, and his FH, while powerful, isn't all that versatile as he can't move his opponent around the court with it. Good players hold easily against him, while they seem to get into this serve games. He can't seem to capitalize on the fact that his opponent should feel a lot of pressure to hold and make mistakes, but his poor return of serve (not enough balls put into play) hurt his chances to break. His movement isn't bad for a huge man, but tennis isn't played in relative terms. Maybe, MAYBE he can win a lot of TBs on a fast USO court with fast balls, but that's doubtful.
Soderling -- average return of serve, and not a lot of variety on serve. On the AD side, he serves out wide too often and his "screwdriver" up the tee doesn't hug the line at all and is easy to return. He is easily put on the run and outmaneuvered because he doesn't position himself all that well and doesn't anticipate well. He does hit some big shots on the run once in a while, but for the most part, his huge hitting can be neutralized if he's put on the run. His biggest problem of all may be that he often goes through spells in a match when he misses too often (first serve and groundstrokes), gets broken and loses momentum.