Man-Spider Spider-Man. Peter Parker as an Oscorp intern who gets secretly selected (because he's poor and no parents and it's Parker Luck) to be their guinea pig for a new super-soldier serum, partially derived from a species of newly-discovered spider. Pete becomes a Green Goblin-like figure, where Peter is constantly battling the violent instinct of the Spider, his body veering between enhanced-human and monstrous-spider-mutant forms as the battle rages between the two psyches vying for dominance. 

Harry Osborne - not Pete's best friend in this incarnation, simply a classmate - discovers Oscorp's doing through documents addressed to his father that he [i]certainly[/i] wasn't supposed to read, and realizes that Peter is becoming a burgeoning threat to his peers (as his behaviour and attitude shift in school) and the city at large (as the Spider vies for control). Heisting prototype Oscorp tech, Harry becomes a purely heroic Goblin (might have to think of a better name), and starts getting close to Pete at school, with the aim of becoming his moral anchor to assist in the internal battle with the Spider, and a role model of behaviour for the Spider itself - or a force able to defeat it as and when the need arises. 

As Pete goes rogue (his changes far outside the expectations of the experiment), Oscorp realize that their stamp is on him at a genetic level, and if he gets captured or killed, medical examination could lead back to the company. Considering Peter a failed experiment, they move on, and commission Mac Gargan, outfitting him as The Scorpion with more tech to put him on an even playing field with the Spider, to put Pete down for good, and bring his body back when he's done. 

When The Scorpion fails (and we'll enjoy a bit of tearing-his-jaw-off reference goodness here), and the tech he was using has to be destroyed to avoid identification (costing Oscorp millions in lost prototypes), they outside contract Kraven The Hunter to do the job Gargan couldn't, while also avoiding any association whatsoever - Kraven being a strict professional. Kraven also does not succeed in killing the Spider, but he [i]does[/i] get tissue and blood samples, a sub-objective of his contract. 

Oscorp run tests on these samples, studying the way Pete's biology reacted to the serum; his mutation was entirely unique, unprecedented even in previous animal and (limited) human trials. With these samples, Oscorp come up with a new iteration of the serum, and test it on two more unwitting subjects; one, a reporter for the Daily Bugle who'd been following the Spider & Goblin story, who'd signed himself up for an experimental medical trial that Oscorp wormed in on, and the other, a death-row inmate who made a deal to commute his sentence in exchange for being a live and willing test subject. Brock takes to the serum pretty well; there's still a split in his psyche, but 'Venom' is far more subdued than Peter's Spider, more willing to work [i]with[/i] Eddie rather than subsume him - he's almost considered a success by Oscorp, if not for his independence and 'Venom's' extreme unwillingness to take orders. Cletus Kasady....goes about as well as you could expect. There's no split in the mind at all, because an entirely new mind is created: Carnage. 

In the meantime, other sub-plots include:
[list]
[*]Miles Warren is an Oscorp scientist monitoring the Peter experiment, and on the forefront of trying to re-capture/kill Peter when the 'trial' goes awry. Attached to the research, he's deeply invested, and this twists a little too hard when, in a rampage, the Spider kills Gwen Stacy, whom Miles was secretly in love with. Off the deep end out of grief, Miles makes killing Peter a personal mission, disappearing from Oscorp along with some of his research, and resurfacing as a self-made monster - The Jackal - with only one obssession: taking revenge on Peter for his lost love. 
[*]Quentin Beck is a narcissist and on-again off-again supporting/background actor-slash-set technician. With delusions of ambition beyond his ability, and failing to get more prominent roles because he's a shit actor, his attention instead turns to the media circus around this new Spider figure, part vigilante part monster, and the Goblin, veering between working with and against him, or just cleaning up behind him. Deciding he wants a piece of the pie, he re-invents himself as a new hero in New York, Mysterio, using his tech and SFX know-how to make some small headway; however, coming up against Peter he is repeatedly embarrassed, and when Goblin has to bail him out the humiliation stings further. Eventually, it's too much, and Beck becomes hell-bent on wreaking revenge on both Spider and Goblin, both for showing him up (unable to recognize this is because he himself is an incompetent jackass, not because they're purposefully sabotaging him) and for hogging the spotlight he believes should rightly belong only to him (because he's a raging fucking narcissist). 
[*]Phineas Mason, AKA The Tinkerer, is the ringleader of a small gang who take on corporate espionage and technology heist contracts, part of their payment always being some of the technology and blueprints for themselves to satisfy Phineas' thirst for designs, and also to outfit the gang itself. When Goblin manages to intercept a heist, Toomes and Schultz get away, but Hardy falters and is abandoned by the gang. As a result, she goes rogue, now hunted by the Tinkerer for her combined failure and betrayal, but also intrigued by Harry as they fall into a will-they-won't-they, Batman-Catwoman, He's-a-hero-but-she's-a-thief-who-also-sometimes-needs-saving-from-other-thieves dynamic.
[*]The eternal simmering-yet-balanced uneasy truce between Wilson 'Kingpin' Fisk and Joseph 'Hammerhead' Martello tips into all-out war when a strange third party - seemingly a small biker gang but ruthless, co-ordinated, and efficient - starts hitting both sides and effectively blaming the other each time. Lonnie 'Tombstone' Lincoln is revealed to be the leader, making a play to shake-up the criminal underworld of New York City while everyone's distracted with the Spider, bringing two secret weapons with him: Aleksei 'Rhino' Sytsevich, a one-man army for Tombstone's gang, and Dmitri 'The Chameleon' Smerdyakov, the perfect tool for pitting each side of the mob war against the other.
[*]Oscorp recognise the Goblin suit/tech on the news and start investigating the heist, interrogating everyone involved with Project Goblin as well as security. One lead engineer gets fired for speaking out and also for letting it go on his watch, especially when he'd been taking home research to work on in off-hours, and basically is set up to be the fall-guy for Oscorp as they shed themselves of anything that could associate them to the vigilante. Furious, the engineer - Roderick Kingsley - turns to his own suit, developed from the research he 'borrowed', to take revenge on Oscorp and Harry alike; but not as 'Hobgoblin', instead adopting the moniker 'Redcap' - a far more violent and bloodthirsty goblin-like creature from folklore.
[/list]