We don't have to do anything different defensively. They may be "comfortable" against the zone, but they don't usually score a lot of points against us. The problem is they are able to completely disrupt our offense. Every time. So in order to win, we simply need to get an average offensive output for this team. How we do that is the question. We haven't played well on offense against Pitt in at least a decade. Think of the wins even, needing a half court shot, needing Jeremy McNeil to go 2-2 from the stripe and then survive several game winning shots that were called off (and that is with Carmelo Anthony on the team!), winning by a score of something like 49-47 in overtime for gods sake.
Play well = Win. But play well vs Pitt is nearly impossible for Syracuse in the modern era.