Though little in 'The Amazing Spider-Man' distinguished Gwen Stacy other than the color of her hair and antagonistic father, Marc Webb would do well to keep her on as Peter's love interest, regardless of her dark fate in the source material. The two already have a rapport, bonded further by their shared patriarchal tragedies. Might as well stick with what works.
News of 'The Amazing Spider-Man 2's' search for a Mary Jane, however, indicates a desire on Webb's part to walk in the same footsteps as the Raimi films. But! What if he brings Mary Jane on only to killer her instead? Now that would be something!
Webb was smart to use the Lizard in his Spider-Man film. Not only had Raimi failed to utilize the villain, but he teased him for three films with his inclusion of a perfectly sane and happy Dr. Curt Connors. Plus, The Amazing Spider-Man's fight scenes were the best part thanks to the Lizard, albeit in a cheesy b-movie fashion.
Sources say Webb wants Electro for the sequel (maybe even played by Jamie Foxx!). That bodes well. Seeing Spider-Man fight a guy who controls electricity provides Webb with an opportunity to go places with these fight scenes that Raimi never got around to.
Crossover With Another Marvel Movie
Legal issues keep this one from becoming a reality. Most Marvel characters are either tied up with either Disney/Marvel or Twentieth Century Fox, while The Amazing Spider-Man is a Sony jam. So Webb has little access to the many characters that would make a crossover interesting.
Almost, anyway. Sony does have their mitts all over Ghost Rider and characters directly associated with that property. So, if Webb really wants to do something beyond Raimi's efforts, he need only provide some seriously awesome Spider-Man/Ghostrider team up action.
Skip the %22Spider-Man No More%22 Storyline
Tempting though it may be, one thing Marc Webb should avoid with his Spider-Man franchise is any attempt to do a story where Spider-Man briefly gives up his superhero life. For one, it's a sort of a cliche in it's own right. But more than that, Raimi knocked this one out of the park with Spider-Man 2, arguably one of the best comic book movies ever. Going up against that would only raise likely unflattering comparisons.
Finish the %22Peter Parker's Parents%22 Storyline
Whatever it was Marc Webb was shooting for with this added business with Peter's dad in The Amazing Spider-Man, it was at least different than Raimi's films. So he might as well see it through and hope it lands us somewhere interesting.
From the little we see in the film and bits from trailers that were ultimately excised, I gather that Peter's dad altered Peter's DNA as a baby in such a way that set up his super powered reaction to that spider bite. Or something like that. It's basically the plot of Ang Lee's Hulk film. But it's nothing like the Raimi trilogy, and that's what counts here.
Double Down on Grumpy Peter Parker
Andrew Garfield definitely gave us a more grumpy, less altruistic and innocent Peter Parker than Tobey Maguire's take on the character provided. While that may have made him less easy to root for, it certainly helped distinguish Webb's version from the Raimi films (though he does at times resemble the third film's Emo Peter). They might as well stick with it. People didn't seem to mind, even when Parker ended the first film flippantly breaking a good man's dying promise.
Or, if Marc Web and Andrew Garfield don't want to go any further in that direction, they could always do the opposite and hit harder on Spider-Man's well known penchant for wisecracking. Raimi's take on Spider-Man had only a minimal use of wisecracks. Webb's version did a little better, though Garfield's delivery kind of comes off as mean spirited. There's a big opportunity here for Webb and Garfield to hone this one core characteristic of the character and make it their own.
Along with the "Spider-Man No More" rule, Webb should also probably stay away from J. Jonah Jameson. While undoubtably a crucial part of the Spider-Man mythos, the Raimi films kind of own this character thanks to J.K. Simmons impeccable and iconic portrayal. It would be hard to see anyone else in the role. The only way Webb could probably pull it off, in fact, is to somehow get Simmons back, which would be weird.
While Raimi's third Spider-Man outing was marred by its overabundance of villains, a Secret Six team-up could actually be one of the coolest comic book films ever, and if done right would provide just the thing to give Webb's series an identity of its own.
There have been many iterations of this group but the original seems best: Doctor Octopus, Electro, Mysterio, Sandman, Vulture, and Kraven the Hunter. What could make this really sing would be to make it an origin-free team movie more or less like The Avengers and forgo Peter Parker's perspective all together. This will never happen, I should add. But that doesn't mean it wouldn't be cool.
The bottom line is this: To help distinguish his Spider-Man series from Raimi's, Marc Webb has to do something big and bold with this next film. Bringing back well-mined Raimi characters like Harry Osborne and Mary Jane is the opposite of what he should be doing, unless he's bringing them back to just to shock us by killing them off. Webb needs to provide an unpredictable, exciting experience and he'll have a hard time doing that if he sticks to retelling stories we already know. You can maybe get away with some of that for your origin film. But Webb's in sequel mode now. It's time to drop some bombs.