For Aunt May, it would be a huge shock. She has already lost so much in her life, and Peter running away would make her feel like she has failed in some way as a guardian. She would probably be constantly looking out the window, hoping to see him come back home. Also, the villains in the story could see his absence as an opportunity. They might become more bold and start causing more chaos in the city, knowing that Spider - Man is not around to stop them.
Spike would be heartbroken. He's like Twilight's little brother. He depends on her for guidance and love. If she runs away, he might try to find her on his own and in the process, grow up a bit as he faces challenges alone. He could also feel abandoned and struggle with his own self - worth.
It could make Batman more determined to find him. Batman would be worried about his safety and would start an intense search. He might also feel guilty, thinking that he could have done something to prevent Tim from running away.
The bond could also make his relationships more complex with his enemies. Some villains might see him as an even greater threat when he's bonded with Venom, while others might try to use the bond to their advantage. And with other superheroes, they may be cautious around Peter, not sure if they can trust the Venom - influenced Peter or if he's still the same friendly neighborhood Spider - Man.
The internship could put a strain on Peter's relationship with his friends. Since he has to spend a lot of time at the internship, he might not be able to hang out with them as much. For example, Ned might feel left out when Peter keeps canceling their movie nights.
It affects his ability to be Spider - Man. Without a stable home, he has no place to keep his suit or his web - shooters. He might have to carry them around all the time, which could be risky. Also, it can make him more vulnerable mentally. He's used to having a home and a family (even if his aunt may be struggling too), and now being homeless can be a huge blow to his confidence.
Time travel could expose Peter to different versions of himself. Say he travels to a timeline where he didn't get his powers. Seeing how his life could have been without them would make him appreciate his abilities more. He might also learn new skills or ways of thinking from these alternate versions of himself, which would enhance his character growth.
It often puts him in great danger. Hydra is a powerful and ruthless organization, so Peter has to be constantly on guard.
The other superheroes in their world could react in various ways. Some might see it as a sign of hope and a new beginning, while others might be concerned that it could make Peter more vulnerable. The villains, on the other hand, might see it as an opportunity to get to Peter. They could try to use Gwen or the unborn baby as bait. This would put a strain on Peter and Gwen's relationships with all these different characters.
For Tony Stark, it could be a blow to his ego. He might see Peter's departure as a sign of failure in his mentorship. He could also start to question his own actions and decisions that led to Peter leaving.
In some fanfictions, it could be that he has made a big mistake. For example, if his actions as Spider - Man led to the harm of an innocent person. He would be so guilt - ridden that he decides to run away from everything, including his friends and family in Queens.