By "most famous," these are judgment calls by Your Faithful Blogger, though I imagine that readers might agree with many of my choices.
Featured below are paintings by Joaquín Sorolla (1863-1923), Gilbert Stuart (1755-1828), Mikhail Vrubel (1856-1910), James McNeill Whistler (1834-1903) and Andrew Wyeth (1917-2009).
This is my favorite Sorolla painting. It has appeared on the cover of a book about the artist, so I suspect others agree with my opinion. It can be seen in the Madrid museum devoted to him. What attracted me to this work is the depiction of face of his daughter, shown on the right.
For some reason, for many, many decades this portrait of Washington has been considered the standard depiction of the USA's first president. A version of this pose is on the state seal and state flag of Washington State, where I live. It seems to be a case of being famous because it was always famous.
Vrubel is well-known in Russia. I'm note sure this is his most famous painting, but it is part of a series he made with the demon as the subject, and that series is probably what he is known for.
Another instance of a painting famous because it has always been famous. What is not clear to me is why it became famous in the first place.
I think most people would agree that this is Wyeth's most famous painting. I believe it has to do with the mood it evokes via its composition (the subject is a comparatively small element in a relatively featureless background) and its ambiguous psychology (one might wonder what the story here is).