This might just relate to me as I use NMM Special Edition as my mod manager and like any mod manager it has it's own little idiosyncrasies.
For me the problem with adding a mod, even a simple esp with no scripts or skse changes is that it changes the load order. This could have no consequences or very significant consequences depending on where in the load order the mod is placed. If I add a mod mid-game I rerun LOOT, redo the load order to my own specifications, I look on LOOT's load order more as suggestion than directives although I usually do not change all that much, and then rerun Wrye Bash.
NMM places almost any new mod at the bottom of the current load order under the Bash Patch which is why it is necessary to run LOOT and Wrye Bash again. The only esm I ever load mid game is USSEP and then I must move it to the original spot in the load order it originally occupied.
I am one of those people who is constantly starting a new game, especially if I get a mod update that requires starting a new game such as LOTD so when I add a mod it does not bother me to redo the load order and start from scratch. I have been playing TESV since 2011 and have completed the main quest and all the DLCs before so I play the game mainly just for enjoyment although one of these days I am determined to get all the LOTD books.