So here's a hypothetical scenario:
I am playing a modded solo game with myself, and my friend Matt invites me to play a D&D adventure.
In order to join Matt's game, I would have to de-activate all of my mods every time I wanted to play, then turn them back on to play solo.
This is a huge barrier to modding. It all but guarantees GM'd campaigns won't really be able to use mods, and strongly discourages people from modding the single player game if they also want to play modded campaigns.
My game client should receive a list of mods when starting a campaign or joining one, and if I have them available, they are activated and loaded.
Stretch-goal: even more ideal would be a system that streamlines downloading new mods so there's no setup. But hey, not even NWN did that. : )