I'd put my foot down and quip, "I'd rather murder you for your irritating, nonstop petulance." Furthermore, I'd quip, "Let's be honest here, you want my wife to leave me because deep down, you're gay and want her in bed which explains why you never had a boyfriend." If that sounds too harsh, maybe talk to your wife about it and hopefully she sides with you and understands that you're tired of her best friend's insolence.

Oh, she's had boyfriends. She's just murdered them all...dunh-dunh-dunh!

That broad is toxic to your relationship. She will convince your wife that she is better off alone, able to party, and be oh so free. You need to be on guard against this, and protect yourself. Toxic women do this regularly, and screw up other people's relationships.