Origin of FF's powers
It wasn't a wave of cosmic rays that mutated them: their spacestation just happened to be close to where Azmuth made some of his early Omnitrix experiments, and the powersurge gave them the powers of Upgrade, Big Chill, Heatblast and Chromastone. Galactus and/or Silver Surfer are the reason the cosmic storm arrived early in the first movie.
In Rise of the Silver Surfer, Reed states that he picked up cosmic radiation from the global anomalies, that share the same signature as the storm which gave them their powers. Thus the two being indirectly responsible for the team's creation, just like in the 1994 cartoon and Heroes Reborn. The cosmic storm gave birth to the mutant race.
During his presentation to Victor, Reed said that a cosmic storm hit Earth long ago and accelerated the evolution of life. If Fox had made both movie franchises share the same universe (which was briefly considerednote ), then this likely would have been true. The man who tried to jump off the bridge would be revealed to have been controlled by the Puppet Master.
Writer Don Payne expressed an interest in the Puppet Master, among many other concepts from the comics. There was also talk about Alicia Masters getting more screen time and her relationship with Thing would have gotten more focus in the third movie, which might have introduced the Puppet Master. The third or fourth movie would have introduced the Skrulls.
One of the concept Don Payne was also interested in. Jessica Alba herself expressed an interest in introducing Franklin Storm. Presumably the movie would have adapted from Fantastic Four #2 (which debut the Skrulls), #31 (which was Franklin's first appearance) and #32 (in which he was killed as part of a Skrull plot), with Super-Skrull being the Big Bad or Dragon-in-Chief. And if they were able to make a Fantastic Four/X-Men/Daredevil crossover movie (since Fox owned all three franchises at the time), then Matt Murdock would have made an appearance as the Four's attorney. After Franklin's likely death, Reed and Sue named their son after him. The thugs near the clothing store Thing broke into in the first film are part of the Yancy Street Gang.
In the third movie, Doom would have become dictator of Latveria, making him close to his comic counterpart.
His defeat in Rise of the Silver Surfer drove him further mad. He overthrows his country's government and military leaders, and replaced human soldiers with Doombots. He began studying magic and sorcery to replace the power he lost. The third movie would have involved the Negative Zone.
Since the reboot featured the N-Zone, it's possible it was intended to be the plot of the third film. Still obsessed with ultimate power, Doom builds a portal to the Negative Zone, in search of power to replace the one he lost (adding to the theory above). He ends up unleashing Annihilus and his army onto Earth. The movie would then feel closer to the comics in terms of the team being explorers of the unknown, as well as having a Darker and Edgier feel (but not in the same way as Fant4stic) since they have to Save the World this time from an Alien Invasion. Galactus wasn't killed.
Silver Surfer merely destroyed his physical form. It might take a while for Galactus to put himself together. It was stated that he'd appear in the Silver Surfer spin-off movie, but it's unclear if it means he returns or only appear in flashbacks. If the former, he may have been revived by his other heralds. Relatedly, Frankie Raye would have become Nova.
Galactus was actually Ego the Living Planet in disguise
A giant power hungry planetary dust-cloud that eats other planets fits Ego more than it does Galactus. Silver Surfer might still have gotten his powers and served the real Galactus, but at some point he ran afoul of Ego, who brainwashed him into finding worlds that Ego could feed on while masquerading as the surfer's true master. It also explains how easily Silver Surfer was able to defeat the dust cloud because it wasn't the true Galactus. In order to beat Galactus you need something on the same power level, while with Ego you need only destroy him as you would a planet. Frankie Raye becomes the Four's military connection.
With General Hager's death, Raye is promoted his position due to being his Right Hand Woman. The sinking of Venice is caused by the Sub-Mariner.
Doom would become Sue's Berserk Button in the third movie.
If Doom showed up, Sue would be pissed to see him again, due to him killing her. She would use her powers to strangle him, until Reed talks her down. Doom being Doom, he tells her to keep her temper and joke where was that fire when she worked for him.