2. Jessica Drew, Spider Woman
In the comics, Jessica Drew (the original Spider Woman) was experimented on by her scientist father and given spider-like abilities. Later on, the evil group known as HYDRA kidnapped Jessica and they brainwashed her into becoming one of their elite assassins. She clashed frequently with S.H.I.E.L.D. while a member of HYDRA, laboring under the misconception that HYDRA was an organization determined to do good in the world and S.H.I.E.L.D. was the evil group bent on world domination. She was ultimately un-brainwashed by the Fantastic Four after a botched attempt at kidnapping The Thing's girlfriend and ultimately became a S.H.I.E.L.D. agent. There are a couple ways Agents of S.H.I.E.L.D. could incorporate this story into the show. They could stick close to the original story by introducing the Jessica Drew character and telling her story with some of the more far-fetched or unfeasible due to rights issues removed, which I would be perfectly fine with. They could use Skye as the Jessica Drew stand in and make her backstory fall in line with the origin from the comics with a few alterations thrown in. Or, they could do a flashback episode using Melinda May as the Jessica Drew character with her origin being that she was a former brainwashed HYDRA assassin who went on to become S.H.I.E.L.D.'s one-woman-cavalry.