Very small things can make a very large difference. I learned the hard way that one difference between MySQL 5.1.68 and 5.1.70 is that 5.1.70 would spontaneously restart if one of my applications added too many new connections quickly.
Keeping all of the packages, their dependencies, and their patches locked down can be overwhelming. This has given rise to the fairly common use of the so-called "Golden Image." The idea is that you get a VM into a state where you know it will perform in a predictable manner and you snapshot it as an image you can create new VMs from.