What is the significance of this painting?
Based on its location in the game (inside the St. John household), it seems to be a subtle hint at the true nature of the family.
Since the St. Johns cannibalize people in order to survive.
This comment actually points out that there is a second painting in their house that is also foreshadowing the rest of the episode:
Some hidden things I found were paintings in the house of the St. Johns. One depicts the last supper of Jesus (Last supper, heh)
I'm not quite sure about its significance in Episode 4, though. The ability to interact with it is especially confusing.