Good stuff Craig. A few things I'd like to mention/add if you don't mind?
I beta test for a few plug companies and have really put some insane time into these things. One of the most helpful things I have ever done was to condition the signal BEFORE you literally go into the plugin. One of the things I hate about plug amp sims is they just do not feel like real amps to me no matter which one you use. (Although I think AcmeBarGig "Headcase" is one of the best as far as the feel option goes)
The other thing that has always bothered me was you can get insane gain out of these plugs yet very little sustain. I'm not talking about cranking up your monitors to the point of feedback, I'm saying these things are hurting in the sustain area to where they just seem fake.
To eliminate both of those problems, you can insert something into your line to bring things to life a bit. Some guys have those cool DI boxes that do more than just DI while others will DI and then run into a compressor. I like that method the best as well as inserting a pedal in line like a Ibanez Tube Screamer or a Boss Compressor Sustainer (the blue one)
Now the key here is NOT to use the pedals for drive/distortion but to boost a little. For example, if we were using the TS, we'd start with all the knobs off, crank the level/output of the pedal all the way up or until it hisses (that's another cool thing...the TC and the CompSustainer are very low noise used this way) and either leave it as is, or slightly increase the gain on the TS IF you absolutely need it. Me personally, I never raise the gain. I may mess with the tone knob on the TS and may drop the output/level to 3/4....but I usually leave the gain set to off.
The same with the CompSustainer. Level all the way up, gain all the way down, set sustain, tone and attack to taste while trying to keep them all as low as possible. The little boost here is us simulating what would be sort of happening in the input of an amp. When we play into an amp, the signal that goes in is buffered/slightly conditioned so that when it hits the amp, it's alive and full of energy. These amp sims lack this liveliness and energy to me...so these little tricks can really bring them to life.
So to recap, it's nice to have a hardware compressor handy to keep your DI signal in check. Sometimes this compressor is good first in the chain, other times it's better when it is second in the chain AFTER the pedal. The pedal just boosts the signal a little bit which in turn gives you actual sustain that won't die out on you as fast. I posted something on this forum a few years back showing you how it can make a difference for the better. It just gives you that little extra "zip" in the tone when using sims and will make a HUGE difference in note hold sustain. That I promise you. It will also force you to use less gain on the actual plugin which will make for a tighter driven sound.
A +1 here on Craig's advice on the low pass. However, (and this isn't meant to go against you Craig, I swear!) us guys that are into the insane high gain stuff wouldn't get the cut we needed if we low passed to 5k. The tones guys like us need start to get their buzz character at 4-5k so if you low pass that far down, you will definitely notice a honky, lack of sizzle type sound that just may not fit thar "heavy" style of music. For classic rock, jazz fusion, country, light gain and just about anything else, the low pass method in that range is essential. But for we that are rock monsters with gain that rips the flesh off of your bones, you may want to low pass at around 7-9k instead. Most people might say "you won't even hear it Danny!" Oh yes you will...it will take the excessive "sizzle" that you DON'T need out of the sound while still giving you that presence to cut through the mix.
At the end of the day, everything is subjective because it will depend on the individual, the gear, the sound chosen, the conviction applied to the instrument...the list goes on and on. A low pass down to 4k may work good for me but may be horrible for someone else. My advice on stuff like this is to try NOT to look at your controls when doing this and see where you end up. When I high pass, I'm not paying attention to the low end frequency I end up at. I high pass until the low end blanket disappears from my guitar tone. When I low pass, I try not to look at the frequency. I low pass until the abrasiveness leaves the sound while still keeping a little "zip" in the tone so it cuts through. :) At any rate, I hope some of this is helpful and adds to Craig's awesome and most appreciated advice. :)
-Danny