There are some really nice options I like in the custom difficulty settings that I like (like hiding a lot of the automatic rolls amongst other things) but are not available to me as my 40+ hour save was started before Patch 5 dropped with the new custom difficulty setting.
I think it would be really nice to allow people to switch over and customise the different aspects even after starting on one of the three original difficulty presets. This would be great for people with tens to hundreds of hours in a save already started before Patch 5 came and have too much time invested in the save to restart just to adjust a few things. It would also be great for new players overwhelmed by all the options presented, or don't know enough about the game and all these options would impact, this way they can start on one of the preset difficulty levels and then later switch to custom to tailor it more to their liking.
I think being able to change to custom difficulty mid-game would be great for player choice and make the custom difficulty less daunting as you can change to it later after getting a feel for the game instead of having to confront it as your first choice when starting for the first time.
