Imo the best FO villains in order are:
1) Frank Horrigan (FO2)
2) The master (FO1)
3) (Shared) Lanius + Benny (New Vegas - By Obsidian)
Just my opinion. Feel free to share your list. As for the discussion itself, I'm wondering if Bethesda will finally succeed in creating their first fleshed out villain. The villains in FO3 were imo really shallow and poorly written, as well as poorly implemented in a lacking story. Yes - Bethesda is more known for great world building, their writing was never strong. In fact - I'd say their strongest villains were in Morrowind.
My hope for FO4 will be that Bethesda finally manages to create a solid FO villain, one that can match Frank Horrigan or the others mentioned above. IMO a story/game is no better than the main villain. The main villain/villains is a very, very important narrative tool to get the character personally invested in the story. What do you think? Will Bethesda finally come up with a solid villain? How important do you consider the villain/s in the story personally?