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During the "Dead City" level the Ark Survivour comes across an absolutely massive mutant modified by authorty tech that makes it immune to almost anything he can throw at it. Fortunately, he just came across a rocket launcher which allows him to fight and eventually kill it. This battle is easily one of the most satisfying moments in the entire game.
The end of the Scorcher's DLC. After the anticlimax of the main game most players probably weren't expecting too much heavy resistance as they stormed the gang's temple for the final level. Then, during the last section a large airship with tons of firepower and armor shows up and gives the player a proper end boss battle. Throughtout the fight the thing sends out air troopers while blasting away with its main guns, leaving the player to take constant cover and pull out the big guns just to survive. After finally taking the massive thing down the player and his new lady compainion then head back to Wellsprings for a well deserved beer and recieve a house/trophy room from the mayor as thanks for saving the town. Truly an awesome ending to an awesome DLC.