if, like me, you care about getting all the talent points, extra health and spirit from each story difficulty (basically anything that affects your character), here is a quick guide on how to do it fast. Note that you dont actually need to pick up the quests from the npcs, when youre in the correct zone the quest just gets added to your log.
Disclaimer: this assumes you have at least 1 character that has done story mode normally, and has most of the teleport points. This is mainly for ALT purposes.
Now then. First, do the prologue as usual. Go to the bank, just rush to Blackcat and kill her and everyone despawns. Go to Avengers tower, do the raft
Chapter 1. Change to your "main" hero, teleport to Abandoned Subway (you cant port to the club because you cant change characters there), exit the subway, change back to your alt, enter the subway, kill shocker -> exit subway into the club, rush through warehouse, kill doc ock, grab the Tablet (25 health reward)
Chapter 2. Change to your main, teleport to the cargo freighter, exit, change to your alt, walk back in and clear it, go back to maria hill in Avengers tower (1 power point reward)
Chapter 3. Change to your main, teleport to Bamboo forrest, change back to your alt, dash your way north until you find the alcove with a canoo/boat outside, go inside the instance, clear it for 5 spirit bonus. Press B (default) to port back to your base, change to your main, teleport to Hand Tower, exit, change to your alt, go back in, rush through ignoring all the ninjas and just kill elektra and grab the tablet
Chapter 4. Change to your main, teleport to Upper East Side (THIS IS OPTIONAL, if you dont want the retcon potion skip this), go to the police station and kill bullseye (retcon reward). Change back to your main, teleport to Fisk Tower, exit and change to your alt, clear the tower (as usual just ignore the mobs and go straight for the boss), grab the tablet again (lol) for 1 power point reward
Chapter 5. Change to your main, teleport to Old Trainyard, exit and change to your alt, go back in and rush to juggernaut for 50 health reward
Chapter 6. change to your main, teleport to Command Bunker, exist and change back, rush and kill pyro / magneto for 5 spirit reward.
Chapter 7. Change to your main, teleport to the shield science station, change back to your alt and cler it for 1 power point reward. Change to your main again, teleport to mutate marsh, change back and search the marsh for a instance called Evolution Facility (this is the most annoying part of this guide in my opinion), clear it for 50 health reward. Press B (default) to go back to your base, switch to your main, teleport to Sinister lab, exit and change back, clear it.
Chapter 8. Clear AIM weapon facility because you need to to get access to Hydra Island. Clear Hydra island for 5 spirit reward. Change to your main, teleport to Doom Castle, exit and change back, clear Doom Castle to get access to chapter 9.
Chapter 9. Change to your main, teleport to ancient ruin site. Change back to your alt and go inside after the cutscene for 1 power point reward. Clear it, in Odins palace go to the northwest corner for the quest to go to the canals. In the canals pray to all the gods that the bosses before Malekith instance are dead so you can just walk in, if not you have to kill all the bosses (theres always people around) to get access to Malekith instance (follow the yellow circle quest marker, its usually in the middle-ish of the map). Clear Malekith, go back to Odin Palace, go to the northeast corner for Loki quest. Kill Loki for 5 spirit reward.
Rinse and repeat for Heroic and Superheroic and hats it, this is what I do with every hero. You could ignore the health and spirit bonuses and it would take half the time. But im OCD so I need those too. Hope this helps