So, I'd say treat this exercise like the Ultimate Comics experiment, expect not everyone is a jerk.
1960's
For the swinging sixties we'd get into the rise of superheroes
Major characters: Fantastic Four (more or less the same. I've seen plenty of similar posts putting them in this time period, and I think they would work best in this time frame. I've also seen plenty of posts suggesting the foursome get frozen somehow and end up in present day. Since I'd like to keep this as original as possible, I'd just have them either age naturally or just not have it commented on), Captain America (James Munroe, yup former Bucky of the 50's just grows up and puts on the costume which he'll wear until a certain story in the 1970's but more on that later), Dr. Strange, Ka-Zar, the X-Men (first line up), Silver Surfer, Dr. Druid
UNCANNY X-MEN, FANTASTIC FOUR, AMAZING FANTASY, TALES TO ASTONISH, JOURNEY INTO MYSTERY, TALES OF SUSPENSE
1970's
More supernatural shenanigans
Major characters: Spider-Man (Peter Parker), Daredevil, Black Widow, Hercules, Ghost Rider (Johnny Blaze), Dracula, Werewolf By Night, Moon Knight, Howard the Duck, the Defenders (Dr. Strange, Silver Surfer, Namor), the Champions, Nomad (Jack Munroe), Captain America (Roscoe Simmons, who has a slightly longer tenure here but falls in the line of duty all the same), Man-Thing, Kickers, Inc. (yes, a team from the New Universe. A bunch of off season football players have adventures. Why not?) X-Men (second lineup, Storm, Nightcrawler, etc.), the Punisher, Jessica Jones, Tagark the Leapord Lord
AMAZING SPIDER-MAN, DAREDEVIL, CHAMPIONS, DEFENDERS, GHOST RIDER, TOMB OF DRACULA, MAN-THING, HOWARD THE DUCK, MARVEL TEAM-UP, MARVEL TWO-IN-ONE, KILLRAVEN, SHOGUN WARRIORS, GUARDIANS OF THE GALAXY, LUKE CAGE: HERO FOR HIRE, IRON FIST, THE ETERNALS, THE PUNISHER
1980's
Major characters: Captain America (Jack Walker, who ditches the suit to become US Agent), Earth Force, Crystar the Crystal Warrior, Wolverine, Alpha Flight, Excalibur, New Mutants, Power Pack, X-Men (third lineup: Kitty Pryde, Dazzler, Longshot, Magneto, Phoenix, Psylocke), Firestar, Captain Marvel (Mar-Vell), Ant-Man (Hank Pym), Wasp (Janet Van Dyne)
POWER PACK, CRYSTAR THE CRYSTAL WARRIOR, ALPHA FLIGHT, WOLVERINE, NEW MUTANTS, EXCALIBUR, HEROES FOR HIRE,
1990's
The time of EXTREMMEEE and pouches
Major characters: Jack Flag, Free Spirit, Vagabond (in lieu of Captain America), New Warriors, Cable, Deadpool, X-Force, X-Men (Rogue, Gambit, Jubilee, Bishop, Cannonball, Sunspot), X-Factor (Government run mutant team), Generation X, Slapstick, Ms. Marvel, Skrull Kill Krew, Nick Fury, Agent of SHIELD
NEW WARRIORS, DEADPOOL, GENERATION X, X-FORCE, X-FACTOR