The collection includes a two issue disaster movie-esque arc, an annual focusing on Jackpot, a rather unremarkable done-in-one, a two issue arc dealing with Harry Osborn's return and past and an one issue character study of Betty Brant. The only real constant between any of the issues is that Mark Waid or Mike McKone worked on it, which is true for all but one of the issues. Other than that, there is really nothing to tie the issues together other than that they are in sequential order.
Red Hulk eventually kills the Hulk then procedes to not only kill the rest of the Defenders but the Offenders, as well, and then the Psycho Man and Dormammu (who where added to the game to make it more "interesting"). Next he tries to kill Galactus, taunting him with the fact that HE PUNCHED OUT THE WATCHER, and while Loeb thankfully thinks better of that, he then has Red Hulk BEAT THE GRANDMASTER TO DEATH WITH HIS BARE HANDS. Question - How does a character like Red Hulk beat a cosmic-level character to death with his bare hands? I mean, seriously, this isn't rocket science or anything but come on, use some common sense damnit! Well, common sense that works for superhero comics anyway.