With my system, I have to shuffle DLC constantly. My upper library limit is about 1700 - after that, enumerates get exponentially longer, Rocksmith starts crashing more often, and I experience "hiccuping" mid-songs.
Enumeration just creates a file that is pretty much a text file with a proprietary format for rocksmith. Yes the more songs you have the longer it will take for it to do that. It should never effect game play once it is done. If anything it would effect when you're going to pick a song having a huge list. I have a 3000 song library and my enumeration takes about two minutes. If you are having game play issues it's not because of your library size.
I'm using a six year old system. AMD-A8 APU with hybrid crossfire and only 4GB of RAM. On top of my library I stream on Twitch and the game runs at the full frames 1080p with all the settings maxed out. Also by the way I'm not trying to be confrontational about anything. I'm just trying to logically figure it out since no one knows how UBISOFT programmers wrote the code that handles this and everyone seems to have different experiences.