I do think the Pats can overcome the losses of Wilfork and Mayo. Joe Vellano and Chris Jones have stepped up in recent weeks, and while they're certainly not Wilfork, they're not going to break our defense (and Jones has small-sample-size-proven to be a better pass rusher than either Wilfork or Tommy Kelly). Losing Mayo sucks, but having Spikes and Hightower should be able to mask a lot there, and I'm pretty confident in Jamie Collins getting caught up to speed by the end of the year. Again, Collins isn't Mayo, but a Spikes/Hightower/Collins unit should be just fine.
The problem for me is Talib. He's the one irreplaceable player we have on D, Wilfork and Mayo included. He has taken away opposing weapons in nearly every game this year, and we're not particularly deep at CB. Plus, unlike with Vellano, Jones, and Collins, the depth at CB is mostly a known quantity-- it sucks. Arrington has been so hit or miss, and while I like Dennard a lot, he's not a lockdown guy yet. Hopefully Logan Ryan can continue to step up. He's looked pretty good in flashes this year. Again, though, none of these guys will be the every-down premier CB that Talib has been.