The Green Bay Packers and Denver Broncos both switched last season, and both squads finished in the top 10 in total defense. The Packers finished second overall while the Broncos were seventh under Mike Nolan, who is now the defensive coordinator in Miami.
The Bills will face difficulty with the same things that all 4-3 to 3-4 teams face: 1) finding a nose tackle and 2) finding guys who can play outside linebacker in the 3-4.
As far as outside linebackers go, the Bills should be okay. Chris Kelsay (6'4, 261) and Aaron Maybin (6'4, 250) are the perfect size to play outside linebacker in the 3-4 and should face a fairly easy transition from having their hand in the ground to standing up.
A lot of defensive ends say they like standing up and rushing from a few yards back because that head start will always be to their advantage against a bigger, slower, and usually less-athletic offensive tackle.
The problems comes at finding a nose tackle. The biggest and best defensive tackle they have, Marcus Stroud (6'6, 310), is probably not big enough to hold down both 'A' gaps by himself. However, if the Bills use him in the same manner as the Cowboys use Jay Ratliff as a one-gap player, he could be very effective.
They will have to find guys who can play defensive end in the 3-4, and could target someone like Richard Seymour who will be hitting free agency regardless of the status of the CBA.
It will be a difficult switch for Buffalo and its success will hinge upon the front office's willingness to go out and get the guys needed to make it work. If not, it will be another long year in western New York.