1. There are a group of Ghouls who have hidden out under the city for years whom you could choose to help and in turn they could help you find the person you are looking for.
2. The person could be a rich treasure hunter who has reason to believe there is something valuable in the city and traversed into the area with a team to find the area more dangerous than they thought, as the only survivor he/she finds a place topside to radio for help. Maybe they don't do it soley for the money but the thrill and hires mercs to help his missions. Hell maybe when you find him he's some weird Feral Ghoul hybrid who is just luring people into the city for prey!
3. Some Ghouls have mutated differently because not all we're exposed to the same amount of radiation, some in the city just turned into Ghouls while those closer the plant went feral.
4. You would run into a dozen or so wreckless merc's who are also looking for a good payout, there could be double crossing involved and maybe some companions. You would have to choose who to trust. The mercs could be really tough as only someone crazy would respond to the signal. And obviously there would be other enemies to fight other than Ghouls like radiated animals or Super Mutants somehow, not to mention other Mercanaries. Also you could run into survivors of the treasure hunter group. Maybe new Feral Ghoul enemies also? Bring back Albino Radscorpions?
5. Also the area would be extremely dangerous so you would have to strategically map out your plans and routes to take.
6. How you could get to the city I have no idea, would it be possible for Ghouls to travel far enough to whatever city would be close enough to a nuclear facility? I have no idea. But considering Zion National Park is over 150 miles away from Las Vegas and you and a caravan travel to it in 5 seconds it's not really that big of a stretch.
1. Do they need help to get out of there or to get to this treasure that the rich guy is after before he finds it?
2. Hmm, could he be an operative of the Shi? Maybe they got a hold of pre-war data from encrypted old world bunkers who states that most of the Hei Guei suits collected from the war at Anchorage was sent there for studies to reverse engineer the suits? Since they don't want to be part of NCR's lands they want to find a way to get the upper hand on them but they need a certain extra edge to be able to hold off NCR and stay independent, the Hei Guei suits are the answer to this.
/idea3. http://fallout.wikia.com/wiki/Endless_walker
4. NCR figured out the Shi's plans and have hired their own mercs but after leaked intelligence certain independent contractors have hired mercs of their own turning the previous ghoul town into a merc war which has disturbed the previously docile feral ghouls. Now it's a death zone with mercs shooting anyone who isn't them on sight along with feral ghouls roaming the streets trying to kill everything and turn their city into a quiet boneyard once again, with the few intelligent ghouls remaining turning increasingly more paranoid towards outsiders and mercs especially, some of the more peaceful ones being trapped in the city as they fear they will get shot among the feral ones by mercs trying to leave.
/idea5. Radiation, buildings and bridges that can collapse, feral ghoul hot spots?
6. Well the Vault Dweller and Chosen One walked for miles in the games, hell, one quest in Modoc has you going to The Den and back to Modoc, the travel time for this is an entire month. So I think meeting up with the merc like we did with Happy Trails would be enough.
(You're contracted by Shi to find their lost operative and to secure the Hei Guei vault, once you've entered you can choose to team up with other merc groups or play them all against each other, or you can shoot everyone around you and go for the vault yourself.)
/idea