The IPOD interface is especially female friendly...that goes for Itunes as well. I bought a 30gb version for my wife and she absolutely loves it. The interface is so straightforward and colorful. Plus, you get album cover art displayed while songs are playing, but also in large format displayed in the Itunes library, which looks very cool. Personally, I like Cowon MP3 players, but they are more technical, therefore, male oriented, and no where near as user friendly as the IPod.
Along with the IPod, get her a pink
Z cover (http://www.zcover.com/) to go with it.