Id recommend the 4.2s for most people.
I have the 5.1s, and they are nice. But the 4.2s would be cheaper and more useful for most people. The center channel I have doesnt get used that often. If Im watching movies or playing Americas Army I use it, but other than that its quiet.
With the 4.2s you have 2 subs, so if you position one in the front and one in the rear, you get a nice "surround" effect with the sub, really nice for the helicopter scene in the Matrix. The center channel you dont get with the 4.2s isnt really too much of a loss since a "phantom" center is created by the front speakers.
If you are mostly getting speakers for music and gaming, the 4.2s are a better deal IMO, especially given the price difference.
Edit: the sats are different, the 5.1s (and the 4.1s for that matter) handle more wattage than the 2.1 sats. The sub also handles more wattage than the 2.1. Of course Ive never found 5.1, 4.1, 4.2, or 2.1 Klipsch sets to lack enough power, so Im not sure how much any of that matters.