It's a little late to be responding to this thread, but I figured I might just to share my experiences as a guitar player who used tube amps for decades that recently moved to mostly internal amp sims in Logic.
The most important thing when running an amp sim that I have noticed is that the signal feeding the amp sim needs to be as loud and as clean as possible. Before I play through the amp sim, I always check the raw signal to make sure there is no audible clipping and no (or at least minimal) distortion artifacts when playing the hardest; usually when playing power chords with a hot bridge humbucker, or just the bridge pickup in general. The reason for this is that the amp simulator is providing the clipping character and any kind of mangled signal going to the simulator will only be further distorted. This isn't the case with a real tube amp, as the preamp section initially is what provides the first clipping in the signal chain, which is much more musical than digital or even solid state clipping with a high quality microphone preamp. if the signal starts clipped before hitting the amp sim and then gets clipped more in the amp sim, it sounds almost like a tone control is rolled off the guitar a little bit and the "stringiness" is diminished. Some interfaces are better at keeping this preamp signal clean than others so be sure to check that raw signal before moving on to the simulator.
A pretty interesting work-around I have found with the old UAD Twin I had was using a DI of some type to feed the microphone preamps and this gave me DRASTICALLY better results than the internal Hi-Z input the Twin provided when using amp sims. This is sort of an industry standard for bass, but in this application, it works exceptionally well iwth guitars. Just make sure that if the DI is passive that it has some kind of buffer driving the DI or else you might have a poorly matched impedance from the guitar going into the DI.
Hope that helps! All the best!
Travis Young.
James C Burlakos