Don't we already have this show? Isn't it called
Fringe? While the idea is interesting, and getting Joss Whedon back on television sounds great, the end result for this type of show would undoubtedly be a police procedural of some sort (of which there are already too many), only with the occasional mention of some minor named villains and heroes. I don't know if that is enough to keep the geeks involved or draw in the average viewer.
That being said, A.I.M. and HYDRA would undoubtedly be the main villains of the series.