I don't mind seeing more of Spider-Man going up against regular thugs in drawn out gun/fight battles, but not a story angle surrounding it that combines The Lizard. You have to keep that type of thing seperate from The Lizard. I don't want to see a soft ass caring Lizard. At least not when he's in full transformation. Perhaps when he's half way through his transformation, we can see his love for his family and such. But not when he's full bleed Lizard, I don't want him to give a damn about his family. Unless he has eyes on them for his next meal.
Nothing is greatly reduced because of a video game. The Lizard wasn't the star of that game, neither was Kraven. The SM4 game will just feature a bigger story-arc around The Lizard. Plus, they're always adding new characters that has nothing to do with movie to the game anyway. Not to mention, that The Lizard/Kraven were not movie versions in the game, so it's moot.
However, if they didn't use Kraven, and there had to be a secondary villain, then I would go with Electro in a seperate story from the Lizard's. Having Electro breaking into a prison facility, releasing more than half of the prisoners inside, with prisoners getting hold of gaurds' guns and causing mayhem. And this will give you more of Spider-Man doing battle with regular thugs in an all out fight and gun battle. First, Spidey takes down the prisoners, then Electro, then The Lizard as he reaches his full transformation.
Personally, I want the The Lizard/Kraven motif for SM4, saving Electro for SM5.