Spider-Man vulnerabilities are part of what make him such a beloved hero. It's much easier to relate to a hero who has typical inadequacies and makes mistakes than it is to connect to a billionaire playboy or a God. Fighting through weaknesses keeps Peter Parker human.
Any superhero knows that the people they love can be used against them, which is why many of them use false identities and wear masks. For Peter, the most effective target to throw him off his game and make him take foolish risks is Aunt May. Peter's poor Aunt has been attacked, kidnapped, and even married a super villain.
During One More Day by J. Michael Straczynski and Joe Quesada, someone tried to assassinate Peter and shot Aunt May instead. Overcome with guilt and grief, Peter threw his life away to save her, making a deal with the demonic Mephisto. In exchange for saving Aunt May, Mephisto wiped Peter's marriage to MJ from existence. In the process, his unborn child was erased too.