SPIDER-MAN has doubted himself before, sure.  But he's also never faced odds like this. One super-powered psyco he can handle, but three?  Before now, he's always had his secret identity to protect him, keep his real life somehow safe and apart from his adventures as SPIDER-MAN.  It tears him apart knowing how Harry Osborn feels knowing his secret, but the fact that Harry has taken to chasing him with machetes isn't much help either.  VENOM seems to know his secrets too,  and takes joy in exploiting them.  SANDMAN is so tangled up in Peter's past that it sometimes seems like he's been living with the guy for years.