1- Fix the unkillable characters bug. Make other ways to finish the game after quest givers are killed. If you should add unkillable characters to the game for other reasons, make it easy for modders to fix it.
2- Fix the engine. In Fallout3 characters movement looks like the game was made in the nineties. They show walking forward animation yet walk backwards, etc... It's first person now, so pay attention to the detail. Add a proper physics engine like euphoria.
3- Make body parts movable like in Vampire the Masquerade - Bloodlines. Make clothes, hair respond to gravity and make it natural. Clipping is the worst thing that can happen to a game.
4- Look at Fallout1 and Fallout2. There used to be tens of junkies dosing in the streets, prosttutes selling themselves, children running around committing crimes. Make Fallout unforgiving.
5- You could become a pormstar with the kama sutra perk in Fallout2. Reintroduce this to the game.
6- And add more conditional perks which effect how some characters and the world respond to you. Your perks could make different characters behave differently to you in the old games. Reintroduce this.
7- High or low luck caused random encounters. Reintroduce them.
8- Intelligence caused your characters speaking to change and the reaction he got. also you could have world changing solutions like advice irrigation to a farmer or find a more rewarding solution to a problem if you had high enough intelligence. Reintroduce this to the game. Perception caused your character to sense whether a person was not telling you the truth or depending on the surroundings and gave you other choices in the dialogue.
9- Fallout1 and 2 dialogues had character unlike Fallout3. Reintroduce this to the game. Not talking about spoken dialogue. Don't really care. I mean the written script.
10- Implement a decent AI to the game and make different creatures or characters behave differently. Make them take cover, escape when appropriate.
11- don't make the game black&white. Make it like Fallout1 and 2 where you had many choices and many of them had further effects. For example if you solve a problem by sleeping with someone low, make our character also gain a sixual disease.
12- Make the ingame music sound more like Fallout1 and 2.
13- Marginally improve the FPS combat. Be perfect in at least one aspect.
14- Make it worth it having a 10 charisma, or 10 perception or 10 agility
15- Make the game bug free. Don't forget things. Never assume the player won't do something. Let me give an example.
In Fallout3 there is a quest where you help a doctor cleanse the caves of fireants. You have a choice to kill or not kill the queen ant. If you don't kill the queen and return to doctor, He thanks and goes into the cave. After that he becomes a mindless junk. Because of a shortcoming of the game engine or something which was overlooked, he starts running madly in the cave because there is a fireant queen in the vicinity and he is fleeing from it. These are very unprofessional things which kill the immersion.
Check http://fallout.wikia.com/wiki/Fallout_3_bugs and never ever overlook these kinds of things. I still couldn't finish Fallout3 due to bugs I encountered. This is serious.
