This is the most important rule. If you install a mod before defeating Mom for the first time on a save file, the game will permanently disable achievements for that save file. Always beat Mom (the boss in the depths) at least once on a save file before enabling any mods.
Given the finicky nature of manual installation, the community standard is (Risk of Rain 2 Mod Manager, which has been adapted for Isaac). This free, open-source tool automates everything. How To Install Mods The Binding Of Isaac Repentance