My library was never that big, but I knew people who had ones at least that size and didn't have any complaints, although given your last sentence it may be relevant to note they were all Mac users. The three-column browser view seemed to work very well for "drilling down" in collections, at least for me. (That browser's actually still in Music, even though it's unnecessarily hidden under the Songs view.)

> It always felt like straight up malware on Windows with all the QuickTime update prompts.

I'm not positive QuickTime was the source of an awful lot of Windows iTunes' badness, but I have strong suspicions. :)