The problem with the Tim Story versions is that they were too common denominator. They felt like they should be in the Kids section
There is a bevy of different relationships between the Four that can be explored: there's the romance between Reed and Susan, the siblingness with Sue and Johnny, and the rocky (groan) friendship between Reed and Ben, and at least one of these will play into the plot. There is also an opportunity to bring in more secondary characters from the Marvel universe, and maybe even do some crossovers with other movie franchises or Agents of SHIELD.
As for villains, Doctor Doom has been done, and Galactus / Silver Surfer has been done. Bringing one of them back would be seen as unoriginal, but forgiveable considering how much they were fudged up. It would be like bringing Venom into the new Spider-man series, but with someone who is actually suited to play Eddie Brock. If it were done right, it would be rated R, which I would personally love to see. Besides that, a Skrull war could work for a rebooted FF series, if that isn't already the plan for The Avengers 2.
CAST
Reed Richards aka Mr. Fantastic: Campbell Scott (The Exorcism of Emily Rose)
Or maybe Tim Robbins, or maybe William Petersen if he loses a bunch of weight. Scott was in a Marvel movie last year where he played the other Richard Parker, but it was a small role, and that has never stopped them before. Some may say that they're all are too old, but I would argue that Iron Garfield was in fact too young, and definitely lacked that "smartest guy in the room" presence. The Marvel cinematic universe needs a 'father-figure' leader who is more than just a military mouth, and Richards should be that guy. Listen to the upcoming Episode 3 of the podcast for more on Scott.