Spider-Man: Edge of Time/WMG

The ending will be bittersweet or a downer.
This is a Darker and Edgier work, right? So, depending on your choices, it could be either of them.

Anti-Venom won't be the killer.
I'm just saying Anti-Venom looks like a really generic choice for the killer of Spider-Man. I guess it'll another more minor super villain.
 * He's been confirmed to be killer. The reason he was picked was because he drains Spider-Man out of his powers, and then kills him. However, with a changed timeline, there could always be more than one villain attempting to kill him....

Amazing will die more than once.
Hey time travel is involved and with that strange things tend to happen...

A version of the Sinister Six will appear.
Compromised of villains from the present and the future.

The next Spider-Man game will take place in its own universe.
And it will throw in various aspects of the mythos coherently, unfortunately, the final mission would be a brand new rendition of The Night Gwen Stacy Died.
 * Jossed--unless something else comes out before it, the new game will be a tie-in to The Amazing Spider-Man.
 * It's a tiny bit more complicated than that. While the universe is in the one for The Amazing Spider-Man Beenox still has a lot of freedom in how the game's story is and the origins of villains. So it might as well be in its own universe.

There's a reason there is no mention of Shocker at all.
Notice how he doesn't appear in the campaign or newspapers at all, and yet the henchmen in the present use weapons like his gauntlets. The reason is that Sloan employed Shocker to make weapons for the company.