Possibly. I really couldn't speculate an actual scenario as I don't remember the period well enough atm. It's a decent long while since I read anything about it. All I can say is that you would presume at the least that no Medici would act against the Pope unless it wasn't a guaranteed act of suicide - i.e. I can't see them just lashing out wildly in response even to an assassination, if the result is an obvious Papal curbstomp on them. Maybe you could mess about with the Italian Wars? I know the time periods don't quite match up so you would probably need to start with a tiny rain-drop POD (a simple birth or death change, or two characters never meeting, or something relatively insignificant) and have the ripples slowly spread out, ever-so-gently nerfing the Medici's power so that they never really get it into their heads that they can get a vice-like grip on Rome. Once they've got the Papacy in sight, there's no real reason for them to betray Rome, as the rewards of having a Medici Pope are just too lucrative to turn their backs on.
Just my thoughts, anyway.