With great power, comes great guilt.
In an effort to free himself of a rapture addiction imparted upon him by the heinous Tyler Stone, Miguel O'Hara crossed his own genetic structure with that of a spider, and was blessed with extraordinary powers. That is, if growing fangs, talons, organic spinerettes and gaining the proportionate strength, speed and agility of a spider is actually a blessing. In Miguel's case, it wasn't, really. Dodging the Public Eye, SIEGE, Watchdogs, and a host of bounty hunters and super-types was never his idea of fun.
Now promoted to the top dog at Alchemax, Spider-man continues fighting to make the world of 2099 something he can stand to look at. Of course, being kicked out of Downtown by the Vulture and having to navigate a company amidst the petty posturing of self-important department heads is, admittedly a different type of battle than the futuristic web-head is used to. Still, amid the aftermath of President Doom's fall and the Night of the Long Knives, he presses on regardless; taking it all one day at a time.
It's really all he can do.