Sam Raimi would be interested in making Spider-Man movies for some time to come, but only if he has final creative control. The director of the first three Spider-Man films, as well as the upcoming Spider-Man 4, spoke to Empire about the film, and some of the issues he had with the third film in the series.
"They really gave me a tremendous amount of control on the first two films, actually," Raimi said. "But then there were different opinions on the third film and I didn't really have creative control, so to speak." This reflects many of the criticisms fans had of Spider-Man 3, namely that the inclusion of Venom in the film felt forced to many viewers.
"The best way for me to move forward on films," Raimi continued, "is that I've got to be the singular voice that makes the creative choices on the film."
This strongly suggests that we can expect to see a symbiote-free Spider-Man 4, and suggests that it is far more likely that Spider-Man will tangle with some of his more classic enemies. "I love Spider-Man so much that I'd like to continue telling Spider-Man stories," Raimi concluded. "But only under those circumstances where I think I can honour him."