I haven't yet fully understood how Last.fm works but I'm going to try to learn it the same way you learn to use a new wrist watch: baby steps.
The standalone player application works great on my mac at home but the Linux version segmentation faulted before the music even started so I'm going to use a much more interesting alternative on Linux which is to play Last.fm inside Amarok (which is tonnes better than iTunes by the way). Sadly the pause keyboard command doesn't seem to work.
One thing I do love about Pandora, is the ability to shuffle between various stations/channels. In Pandora I've got one station of heavy metal and one for Frank Zappa type music (amongst others) and if I stay for too long on one station it gets a bit boring. Let's hope this is possible with Last.fm too.