Personally, I was hoping that they would include Ultimate Liz Allan's racism against mutants (or I guess its the Inhumans now), but instead of becoming Firestar, she becomes the MCU Lizard.
Harry Osborn, her boyfriend, would serve the "Damsel in Distress" Role instead of Gwen or MJ because LIZard wants to mate with him.
It would be a huge curveball for pretty much everyone who has ever consumed Spider-Man based media. Have Curt Connors as a red herring, but he receives a prosthetic hand (like the one RDJ gave to that kid, so let's have some story-relevant product placement), and comes up with a vaccine to return Liz to human.
We could set up Liz Allen in a previous film before she becomes the LIZard.
Not nearly enough female super-villains. Could have a Bechdel Test moment where MJ and Gwen are worried that Liz might be cutting herself because she wears a hoodie during a heat wave (to hide the scales forming on her body.)
Could lead to a humorous moment where Harry notices that the monster has the same tramp stamp as Liz Allen. Alternately, Spider-Man notices Lizard has the same Tongue Piercing.
Also, would probably give MCU Liz a plethora of Lizard-based powers that haven't been used in any incarnation, such as camouflage (so Spidey has to use his Spider-Sense to fight an invisible foe), shooting blood from her eyes (because the sewage wasn't gross enough), and finally...
Spider-Man: (Cornering the Lizard on Coney Island with her back to the Atlantic Ocean.) Alright freakshow!!! You've got nowhere to-(Lizard dives over the edge of the boardwalk, Spider-Man rushes to after her and peers over the edge.)
Spider-Man: Jesus Christ!!!
[Cut to Lizard running on water like the Basilisk.]
Anyway, those were my ideas.