Yes, I can tell the difference between 16bit/44khz source material (FLAC and Apple Loseless) -vs- LAME MP3 encoded at 320kps VBS and AAC at 256kps. I could hear the difference with my HD800 being driven by a Lavry DA11, but it didn't take a high end rig. I can tell the difference with my iPhone into Etymotic HF3, or the original SqueezeBox into NHT SuperOne speakers. I couldn't always identify what the difference was, but the lossy almost always sounded "wrong". leaving be feeling somewhat uncomfortable.
It's incredibly simple to do this sort of test for yourself and I would encourage you to give it a try and then let what you hear guide what you do. I wish I didn't hear the difference. My loseless collection doesn't fully fit on my laptop, and certainly doesn't fit on my iPhone so I end up having to actively manage what I sync and it's not uncommon for me to discover I don't have something on my device that I want to listen to. My daughter doesn't really notice a difference, so she is using AAC. Our entire collection easily fits on her laptop, and just fits into her iPod. So she never experiences the "I want to listen to ___, shoot, it's now on this device" and she is happy using Spotify rather than purchasing CDs for most things.
Edited by verber - 11/14/12 at 8:09am