I remember one three-in-one What If where the radioactive spider bit Gwen Stacy, Flash Thompson, and John Jameson rather than Peter Parker. (Three separate stories, not all together.) IIRC, they all ended with each of them dying heroically... and Peter extracting the venom from the dead spider to carry on their legacies.
Though my favorite had to be the Assistant Editor's Month What If, with such bits as "What If Reed Richards never invented unstable molecules", "What If Tony Stark had an eating problem rather than a drinking problem", and "What If all the heroes in New York City moved to Toledo, Ohio." Not that any of that would transfer over to the televised series, but a lot of it made me laugh.