I'm doing a lot with update handlers these days. This is where I put almost all of the configuration changes for a release. Putting configuration changes in update handlers has the huge advantage of (a) source controlling these changes, and (b) allowing you to qa them. I strongly recommend this practice.
Most configuration changes are very easy to make in code. Often all you need to do is call variable_set. Sometimes, you have to write some SQL to directly change a table value.
