In New York City, several hundred people reserved rooms in Vault 154, were the test was to slowly leak radiation over the years in the vault, inducing ghoulification among the residents. After 150 years, the now ghouls exited the vault into the Atomic Apple , were the were greeted by a large group of slavers who who called themselves the Workers(or a better name if you have one). The Workers don't take too kindly to ghouls, and either enslave or senselessly murder them.
After about 50 or so years, the some ghouls start to stand up for themselves and start a revolt that soon becomes an all out civil war. This is where the player comes in and either helps the Workers supress the incident or liberate the ghouls by joining their militia. Some quests and plot would also be included, so brainstorms are welcome!