Madrid is the capital and largest city of Spain.
During one of their very first missions as S.H.I.E.L.D. field agents, Phil Coulson allowed Melinda May to drive his car Lola, making her vow to never tell anybody about it. Years later, a Life-Model Decoy of the real Agent May told this to Daisy Johnson, recollecting that the event may have happened in Madrid.
Hiding from the Hand
Worried that there fight upcoming fight with the Hand would not be the end, but just the beginning of a bigger conflict Elektra and Matt Murdock talked about leaving New York City and hiding under a different identity. One of the possible locations suggested by Murdock was Madrid, Spain.
With the knowledge of the Darkhold Holden Radcliffe and Aida began perfecting the Framework. Upon completion the code had become so powerful that it had to be processed on devices from all around the world. Part of the data was transmitted to six processors in Madrid.