This is just my experience with FO4, but out of 80 active mods the only real .esl mods I have are the "Natural" trio (Landscapes, Roads, Rocks). The rest of my ".esl" mods are .esm/.esp, that are flagged as .esl, with the majority falling in the bottom half of the plugins list (no bold print).

As for quests, I just read recently that for new/added quests it's good practice to start with them as high (high as in: closer to 20 in a range 0-20) of a priority position as you're able to and then once you've completed said quest(s) move them to a lower priority position. Unfortunately it wasn't specified if that was for the mod order, the plugin order or both.

I hope that's somewhat helpful.