A producer of Fallout 4 said that he has played over 400 hours of the game and still has not found everything in it.
In the Fallout 4: Far Harbor (2016) DLC there is a lake and when swimming across the lake you will see two skeletons floating on the lake, one of which is lying on a door and the other is in the water holding on to the door. This is a reference to the famous scene from Titanic (1997).
Fallout 4 contains just over 111,000 lines of spoken dialogue, which is more than Fallout 3 and Skyrim combined. The player's character has 13,000 spoken lines each for the male and female character.
If you find a Globe in the game, you will notice the continent of Africa has combined to form one mega-landform with Europe, the Middle East, and Asia.
This is the first Fallout game in which the player's character speaks, as shown in the reveal trailer.