There are androids.
I saw at least one monster with only one arm - it looked like some kind of mutated horror.
There are swamp people and swamp areas.
Conversation trees are different.
The settlement building function is extensive, BTW - raiders can raid your settlement and you have to build defenses. You actually place walls and furniture where you want it. It was mentioned that was all completely optional though.
Mirelurks look a lot different.
I saw some kind of mutated one-armed monster briefly.
There are android enemies.
Scorpions and molerats can burrow now.
The environment appears to be more reactive - I am pretty sure I saw minigun fire break windows.
The dog can be used to fetch items and the interface to make it do so appeared easy to use.
The UI in general is now contextual.
The weapon modding/crafting function is very extensive and covers all weapon types.
The new armor system is per body part instead of a suit like FO3.
Animations are better.
There will be mods. The toolset will come out later (after the game).
Skills may be out. Perks are still in. People theorize the two were merged somehow. Unsure about traits (from NV). They may be gone.
I saw at least one character with a robot hand. I don't know if he was an android and just lost his "skin" or if it was a person with a cyborg hand.