Well first thing is to learn all you can about the game engine. Study the few documents that are out there. Get yourself a hex editor and start playing around with the code to get a feel for what different changes can do. There is a lot of tedious experimentation involved and for people like me with little programming experience it is very difficult. But you just have to be ready to spend a lot of hard hours testing and experimenting.
Then when you have learned what little is possible, you have to decide how you can use that information to do something interesting. Some people have managed to find the code that controls weapon damage and changed the values. For something like creating a new city in Fallout, there is probably too much for one person to do so you are probably going to have to join a team.