Any advice for maintaining a heavy modded play-through?

[TacticalHotDog]

Hi guys (and gals),

For the last year, I've collected a huge mod list of about 300-400 mods. Right now, I'm in the process of verifying compatibilities before starting the play-through. As this is the most heavily modded play-through I've ever tried, I would love some help and advice before starting so that I won't screw everything up.

Besides carefully double checking compatibilities (which I'm doing right now), are there any pre-playthrough processes that I should do to ensure the stability of my game?

Also, is Merge Plugins a reliable tool for minimizing load order? Because right now I have 400+ plugins (WAY PAST the 255 limit). If so, what types of mods are safe to merge together?

If you guys have any additional advice or tips, that would be greatly appreciated as well. Thanks!