When using an Airport Express your audio, even uncompressed files, are converted to ALAC on the fly within iTunes before it is sent to the Aiport Express. I was using this setup for some time but found I was not enjoying my music as much as I should.. so, I've pulled my library into Mediamonkey and use the ASIO plugin. It does sound better, in my opinion. I have my audio card, with it's audio drivers allowing a bit perfect output via ASIO, connected via a Toslink cable to my DAC.
I've since moved onto another piece of software which I believe takes things a little further by taking into account the fact that other services running on your computer can interrupt your audio. It works to reduce this impact and loads audio files into RAM before playing.
There'll be people that argue that this is overkill, sure. But I swear I can hear a sonic difference. A laid back sound that's just so easy to listen to. The software is XXHighEnd.
In terms of setup the Mac is so straight forward; take the digital out from your Mac to your DAC via USB or toslink. So easy.
On the PC things are more complicated, but a little playing around will give you amazing audio.
The iTunes & Airport Express route is the easy way to get wonderful sound with minimal hassle with all the ease of use that iTunes has to offer. And a large number of compressed tracks do sound pretty good too. Some compressed is pretty hard to tell apart from the uncompressed version.
One could dedicate a whole magazine to computer audio. It's going to take off in a big way. I wonder whether you'll find anybody who has tried it that has turned back...
Lastly, anybody wishing to get into computer audio should take a look at the number one resource on the web for such things:
www.computeraudiophile.com ... Chris, the owner of the website has spent considerable time writing guides on how to setup a great system for little money. Just a quick read through his media servers will be enough to get anyone started, and it doesn't have to be expensive either.