You should go back to a couple days before the nuclear war happened, when your character is a kid, and on the day of the war, he's playing with his bestfriend, over by a lake*, when his dad calls to him and tells him to pack his things they're leaving, as they are getting to a vault, and his bestfriend is not as fortunate to make it to a vault. Growing up in the vault he has no friends, he is completely lonely. About 10-15 years later, as the vault is just conjuring up their experiment to unleash upon the residents, he manages to escape, with his dad. Once they leave, the two of them set out for a settlement of some kind. They arrive at a settlement that doesn't look to shabby, and learns that his bestfriend from when he was a kid, managed to stay alive. Just as you are leaving, a group of bandits come to the settlement and attack everyone they see, just before you kill the 3rd last one, your dad is sniped down by a sniper, and your anger takes over, you have to kill the remaining bandits. After a few short words from your father, you set off. You travel back into the city where you lived, and have flashbacks of when you were a child, and after a while you make it into a settlement inside the city.

You go to the 'governor' in the heart of the settlement and ask him if he has seen your best friend. He tells you, that your friend is there, but is in no condition to see you. You find out that he is mutating into a super mutant, at a rather slow speed, that could end up killing him if he doesn't get the cure for it. After finding out the 'governor' doesn't know where it could be, he tells you to ask the medical supervisor about it. Once you find the medical supervisor, he tells you where he thinks it could be, at the city hospital.

After a long journey, you get to the hospital, and have to search the hospital looking for clues as to where it could possibly be (hack terminal). Once you manage to get to the room, you find out the cure, is not tranportable, and you must bring your bestfriend to the hospital. Just as you're entering the lobby of the hospital, you see raiders, alot of raiders. The leader tells them to search the whole thing for anything, and you have two choices; fight all the raiders, or run and hide, until it's safe to leave. Once you return to the settlement, you find your bestfriend is getting worse and needs to get transported right away. You can tell the 'governor' that he is in desperate need of help, but the place is crawling with raiders and you need men to help, OR that you need medical officers to go with you, as well as a few men to barricade and hold off any threats that may be coming.

A ) If you did kill the raiders first time off, you just go straight to the machine with the men barricading and defending the lobby.

OR

B ) You and the team of men you brought along kill the raiders, and then you tell them to defend it, and get the medical team and bestfriend, to take to the hospital. And also, there would be a side quest to get more men to help you from differant settlements.

Once your bestfriend is hooked up and everything, ready to go, the medical supervisor noticed it doesn't have power. You go downstairs, to seek help from the captain, and find out, that super mutants are attacking the hospital, and that the men are dying, so you must hack the terminal and look for the plans of the building, to find the generator. The PC gets to the generator, finding out it needs a bit of power to power up, so you must get to the back-up generator, in the annex of the building. You find multiple cannibalised humans there, looking for food, and food just walked in the door, you can kill the cannibals or run for the back-up generator. Once you power up the back-up generator, you have to go back to the generator and power that up, but, since doing so, you have alerted all supermutants to go there, and must hurry to help the troops, or quickly restore your bestfriend.

Once you get to your bestfriend, you activate the machine, and he starts to heal. The medical supervisor tells you to get fresh water and food for when he wakes up. You must travel to a spring out of the city, and get water, the go back to the settlement and get a bit of food. Once you get back to the hospital, you realise there is noone alive. The troops are slaughtered and the medical team dead, and your besfriend, gone.

Using clues, you must find out what happened to your bestfriend, and after a while, you find out he broke out of the machine himself. You travel to a cavern where super mutants are living in and must travel into the deepest part of it to find your bestfriend, who is half super mutant, half human, he is bulky like a super mutant, but is not green, he has human thoughts and control. Upon your meet-and-greet with him you share some words, you can either;

A ) Go against him. He then attacks you, and you must fight him. Once you kill him, you must travel back to the settlement and talk to the governor. He tells you all is not lost, and that you must help them rid of the super mutant infestation. Upon doing so, the main story is complete.

OR

B ) Leave him there, once out of the carvern you must travel back to the settlement and talk to the governor. He tells you all is not lost, and that you must help them rid of the super mutant infestation. Upon doing so, the main story is complete.

OR

C ) Join him, you will become a super mutant and can wreck havoc across the map. The story will complete once you become a super mutant. He will also become a companion.

OR

D ) Accept his invitation to become a super mutant but kill him afterwards and lead the super mutants in the battle against the humans.

NOTE
There would be more quests to do so afterwards for the 'governor' and other side-quests.

&

*Character customization. Player looks down at the lake and thinks of himself in the future. & Me and my friend who thought of this, think it would be better to use Detroit or Chicago as the location.

You need to keep suggestions for the next Fallout in http://www.gamesas.com/index.php?/topic/1094022-fallout-4-speculations-suggestions/ please.