The main quest on Fallout 3 is Trouble on the Homefront, after the Waters of Life.
I believe he's referring to Borderlands, not Fallout 3.
There are a multitude of main quests which come up as you go to find the vault. However, there are 4 quests which contain portions of the Vault key. One is Sledge, Two is Krom, Three is the Rakk Hive, and Four is Baron Flynt. However there are many other main missions in the game. If you want a full list go to http://borderlands.wikia.com