This may sound as a stupid piece of advice, i.e. cheapest flight (or the most convenient one?) but I think that anything else I'd suggest would be based on my very personal likings to be really objective. For example, you could combine Athens with one-day tours to places such as Delphi, Olympia, Nafplio/Mycaene and even a close-by island (e.g. Aegina or Poros) but you could equally well go to Toledo when visiting Madrid or to, say, Andora from Barcelona. Granted, as a city
per se the latter is much more esthetically pleasing than the other two. Museums in both Athens and Madrid are absolutely amazing but you may prefer the paintings in the Prado more than the antiquities in the Acropolis Museum. Your choice is basically like that between apples, oranges and peaches, which can't be solved by tossing a coin. Sorry if instead of helping I make your decision more difficult.
