I use a Dell PC (for now) and setting up my iPhone was a breeze. I think I must've been lucky and hit a lull in the proceedings over at AT&T because activation went through in seconds. I thought I couldn't sync my Contacts from Outlook, but they're actually in the Windows address book so, once I switched to that, they synced just fine. E-mail accounts didn't sync, however, so I had to add those manually.
My wife uses an Intel iMac. We knew to update iTunes but they didn't tell us that we needed to update Tiger too. Before we did that, the iMac kept thinking the iPhone was a camera, and opening iPhoto. Once we updated Tiger, the iPhone set up was fine...until we got to the AT&T part and got tripped up by that bottleneck. Activation went through fine this morning.
I have Wi-Fi here at home and the internet is just fabulous on such a little gizmo. Calls have been clear and strong, even on the speakerphone (which you can use whilst docked). E-mail and texting is cool, too.
Not exactly plain sailing in either case, but not too terrible. I wouldn't have wanted my Mum to go through all that, though!