Big things are just make sure you read through all the incompatible changes so there are no surprises (or less chance of anyway), do a mysqldump for the upgrade instead of just an in-place binary replacement (if it all possible), and in a replication environment do the slaves first and then the master (often people just then promote one of the slaves to be the master, and then either upgrade or just rebuild the old master into another slave). These are just mile-high bullet points, but the docs have all the important details. =)