I did a book collection run once. Collect as many unique books as possible in a single run. I got about 94% of the books in the game, which is as many as I think you can get in a single run. The remaining 6% is locked behind story branches that would eat into the 94% I did get.
And honestly? It wasn't that fun. I had to scour rooftops, look around in vases, cross-reference the wiki, reload the game because I made a wrong choice that seemed like a nothing choice at the time... And all I got were some notes. And they weren't even much better than the ones you get in a normal run.
And this was just books. I had to skip Gale's content entirely just to collect an extra note. There is a robe you can only get if you kill Karlach. There's simply too many branches for you to get everything.
You can't get 100%. You might be able to get 95%, but it won't be fun. From now on, I'll just clear the map markers before moving on, and that'll be enough for me.