I have a relatively slow L2TP/IPsec connection (128kbps) that I need to optimize as much as I can. I also noticed that in PPP -> Profiles -> default-encryption, it offers a setting called use-compression. Does this actually work? Both ends are using ROS.

You could enable it on the L2TP server profile and client on both ends, sure. But it won't change much. It made sense back in the DSL 20Kbps era or some other ATM based networking.

Ensure your WAN interface has proper MTU along with accounting for the ghost/hidden 20Bytes hard-coded on MikroTik interfaces: viewtopic.php?f=2&t=171390#p838707

With Proper MTU on all interfaces on both ends, you will get the best possible performance for your link speed to the ISP etc.

Ensure your WAN interface has proper MTU along with accounting for the ghost/hidden 20Bytes hard-coded on MikroTik interfaces: viewtopic.php?f=2&t=171390#p838707

This is insane, so ROS includes 20 extra bytes in each header that they never told us about? That's a recipe for packet fragmentation unless I do what they say and turn the MTU up to 1520.