A lot of why comic book mythos feels so disjointed is because everything's written by different authors. Inside their own run, it doesn't matter too much until another author tries to reintroduce certain plot points and storylines. Some writers do it better than others.

If you were a writer for Spider-Man, how would you group the mythos? Either by timeline, macguffin or nebulous organization.

Here are some of mine:

Spider-Man's First Year:
Struggling scientist Otto Octavius finds the wreckage of an alien spaceship and gets into an accident trying to salvage it. Phineas Mason gets abducted by remnants of the aliens, the Iron Cross Army, that originally were on the plane.

Hydra and the Finisher:
The Chameleon and Rhino are hired by a HYDRA faction to try to steal secrets from NASA Astronaut John J. Jameson, but naturally Spider-Man interfered. Chameleon calls his half-brother Kraven to deal with him.

The Lifeline Tablet:
Kingpin fakes his death to incite a Gang War that would help wipe out his competitors. Silvermane believed that the technology from the Lemurian Tablet of Life and Time will help rejuvenate him to take power. He and his goons experiment on many illegal immigrants and homeless people including a certain Snakehead that tried to cheat them.
When Silvermane succeeds in his quest for power, Spider-Man, the Prowler and Black Cat have to race to find the other six Tablets in order to be able to depower him.

Oscorp:
Michael Morbius, a vampire looking for way to become human, joins Oscorp in order to research said cure. Norman Osborn was a renowned scientist and businessman and a closet occultist who loved to research magical artifacts, so he naturally was fascinated with Morbius' plight. Morbius and Osborn seemed to make a "cure", but Osborn had ulterior motives. He was essentially able to bottle the vampire curse and then began experimenting with it. The run-off ended up causing mutations to people like James Santini and Edward Whelan. Morbius wants to turn on his boss, but Osborn revealed that the cure they made was only temporary, and that if he wanted to stay human, he would have to keep working for him.

Spider-Slayers:
John Jameson's contact with the alien material caused him to begin mutating into a wolfmonster which did a number to his psyche. He killed the mobsters that murdered his mother and then attacked his father due to pent up resentment. While Spider-Man was able to get him back to normal, the appearance that he assaulted John kicked Jonah's vendetta into overdrive.
He funded projects with Spencer Smythe and Marla Madison to try and capture the menace. After the first Spider-Slayer failed to capture him, Jameson decided to make an anti-Spider-Man using Dr. Connors' Neogenic research. Dr. Farley Stillwell experimented on volunteer MacDonald Gargan to create the Scorpion.