At the start, you'll encounter much more tougher enemies that before. On the way, destroy the magnetic shield generators marked with an "X" to have a better chance against Galactus.
Super Skrull and Paibok
Before entering Aeronautics, you'll meet the Skrull Empress and her two henchmen, Super Skrull and Paibok. The Skrull Empress makes a deal to pick either two to go through more enemies to open up the next area. Paibok has strength which is super strong and Super Skrull has the powers of the Fantastic Four. After you unlock the large door, she reneges on the deal and allows her henchmen to attack your team. They're very much a powerful duo. So defeat them in this battle of strength to continue on the mission.
The Cityscape is like a side scroll platform except you really have to stay away from the edge. Also as an option, you can destroy the objects on the core drills by using range projectiles to take it out. At some point, Galactus will turn his attection to you and orders his goons to attack you. Continue on the path until you reach the Heights of Progress.
Titannus Super Madness
Your next boss will remind you of the first game, X-Men Legends, a flashback involving Magneto, barging in to attack Professor X's Mansion. Titannus comes close. So if you upgraded your superhero team, then you have an easy battle ahead of you. Just watch out for his minions that's coming in to attack you. Also before you leave, free the scientist to get the XP.
Escape from Galactus
Galactus, the world devourer, is such a giant, the first thing before you battle him is to escape to a safe spot. That means running as far away from him as possible. If he grabs you, free yourself and continue running in the same direction. The hardest part is the top platform tower that Galactus knocked down that you need to climb up and continue going past barricades and enemies to a safe location. Don't worry about your teammates.
Silver Surfer vs Galactus
Once you reach the final stretch, Silver Surfer, will heal your teammates and ask you to do the following patterns. Go activate three consoles to scramble Galactus' mind. Then you follow Silver Surfer through button sequence or Wii motion sequence so the bomb that Galactus is about to blow will detonate early hurting himself in the process. Do it three times to end Galactus' fury.
Take the portal back to Royal Library with the two items required to defeat Dr Doom. Get Lockjaw to bring your team, Nick Fury, Black Widow, Vision and Dr Pym back to Stark Tower.