I started with the Fender and Orange collection, Sharke and those 2 sold me. I picked up the whole collection last time they did there group buys. I find the Amplitube sims very hard to beat. The best ones seem to be the newest sims, which only makes sense.
I really like the new S Gear, 57 amp they added to their sim collection as well. I haven't used it in a song yet to see how it sits in the mix, but just playing it solo, it sounds awesome. The way these new sims react while I am playing are close enough for me, that I don't notice really that I am playing a sim. Once in a mix, fx, compression, limiting, I think they sound great. I keep having songs forum guys tell me that my tone is really good.
If I played live a lot, then it would be a no brainer to go the Axe Fx route. For me, the little that I play live, my real tube rig and a handful of pedals gets me by, for now.