I think Otto will have a long run as the Web-Head, as confirmed with the new "Mighty" hype going on.
While he is a classic, Spider-Man seems kinda forced nowadays. Most of his main baddies and conflicts in New York have faded. And hes implemented in so many Avengers tales.
So either Otto keeps on rolling, or...
I am thinking he'll have to stop Otto from doing something mega bad by psychic warfare, but it kills both of their minds, in a sense. Then maybe a new Spidey will rise, or maybe he can be put to rest.
Live in a hall of fame of sorts, better than what they did in the Ultimate Universe, but still.