... the databases being written to are multi-user environments and cannot be locked because they are perpetually in use.

Mmm, that sounds like locking is particularly necessary. Perhaps your rdbms system has record locking.

It is hard to answer your question without knowing what these things are built on. You are sucking unspecifically large hunks of data into perl hashes. When memory gets tight, vm swapping is going to wreck performance. You might get better performance from stored procedures, a big redesign of the databases, or slaving some tables, but without specifics it's hard to say what you need to do. Being less ambitious about memory use may be enough to speed things for you.