Before I bought the Spyder 212, I had borrowed a friend's POD and played it through my keyboard amp with so-so results (could have had much to do with the amp).
Line 6 pushes the fact that the Spyder's models are tuned to the speakers (specially designed Celestions) and the cabinet for a very cohesive sound, which I agree with 100%. If ultimate flexibility was most important to me, I probably would gone the Pod/clean amp route, but I chose tonal quality and ease of use and went with the Spyder.