I think differently than a lot of people, I guess... I don't want to just be confident in my decisions. I want to know exactly why I make them. When I hear an anomaly in my sound quality, I don't worry about what it MIGHT be... I grab on like a terrier until I find out EXACTLY what caused it.
I have over a year and a half's worth of music in my iTunes library... classical, jazz, pop... older recordings, newer recordings... all kinds of music. The library plays throughout my house via wifi to every room in the house. The same library serves my main listening room where I have the system I've been refining for the past thirty years.
Every time I've heard a problem with the sound, I've tracked it down. It's never due to lossy artifacting... it might be a bad recording, equalization problem, funky transducer, volume imbalance, a million things. But I've never found a single artifact in my files. I use AAC 256 VBR. I determined that setting by doing line level matched A/B comparison testing.
To be honest, I don't think an audiophile will ever achieve optimal sound quality by taking the "more numbers is better" approach. The problem never has anything at all to do with the file size in my experiience. You can't get perfect sound by relying on numbers to do the work for you. It takes proactive problem solving. In fact, if there's anything I've learned in 30 years in this hobby, that is it.