Did you run a post-PAR (timing) simulation on that? On designs with low timing slack or large area occupation this is really important, otherwise you may easily violate setup/hold time constraints in what are usually very nondeterministic ways. This is, in fact, one of the reasons why ASIC development is ~80% verification.

We had a bug of the kind once, where a Microblaze core would fail to boot the Linux image after what seemed a trivial modification in the peripheral code, but it turns out we were packing the logic so tightly that this change blew the timing on some critical net. Ah, the joys of digital design.