Sin

While there are very few chances that Sigourney Weaver would portray this character, Sin would be excellent. This would connect the Netflix shows to the bigger MCU, as well as to Agents of S.H.I.E.L.D. In the comics, Sin is the daughter of the Red Skull, the first villain of Captain America (on the big screen, of course). As such, she received hand to hand training and she is very skilled.

However, the more interesting version of the character is the Mother Superior version – she has telepathic and telekinetic powers, and she can also become intangible, as well as teleport herself. With such skills, she’d be quite a threat for the Defenders.

More interestingly, Sin is a deeply emotionally scarred character. And if there’s an actress who can bring all the emotions to life, that somebody is Sigourney Weaver.

Even so, the chances for Sin to be the main antagonist of the Defenders series are slim – mainly because, until now, the Netflix shows took on a different path. But I would be happy to see Weaver portraying this character.