Here's the most important piece of advice I can give and this comes from several years (2006-2010) using several Line 6 amps (Flextone2, HD147, Vetta 2, SV MK1).

Dial in your tones.  I tend to converge on a "favorite": Clean, Clean wet, Overdrive, Lead wet (4 total).  I'll have some others in there too like a lo-fi AM Radio tone.  But those (4) are my go-to's.

Anyway, let's say I have them dialed.  It's just me, in a sound deadened room with my amp and cab and at a volume that doesn't require ear plugs (so I can hear the subtleties, right?).

Now, you save them somewhere handy... but NOT in a location you want your FINAL tones to be.

Copy them to where you want your final tones to be.

For example... Bank 1 would be my final, most used tones.  Bank 9 (or the last bank) would be my reference tones.  Make sense?  You have just duplicated them... that's all.  This will make sense later.

Now, flash forward to band practice.  My band practice is 5 guys and a drummer that blasts!  It's heavy and it's loud.

How's your tone?  Garbage, right?  Admit it.  Every time.  Here's why... you didn't dial it in with the band.

I tend to find that my cleans are never loud enough and my overdriven channels are too muddy, too much bass, too much gain, not enough mids, and sometimes too little highs or presence or not enough.  You gotta make mental notes while you are rehearsing with your band.  I know it's hard, but you can't very well make intelligent adjustments in mid song... you gotta wait for a break in the action to make your changes.  Yes, it's time consuming and frustrating at first but realize once you’re dialed... you don't have to do this anymore.  I find I'm done tweaking after the first month of a new amp.

Bare in mind that was just one practice.  You should really continue to dial in your tone for at least 2 or 3 more practices.  Like I said... a month for me to stop tweaking.

Now here's the big pay off....

Compare your live tones (Bank 1) to your original tones you dialed in alone (Bank 9).  Notice the differences.  It's pretty crazy.  You might think Bank 9 sounds better as you noodle around on your own, but once you get everyone in the room and playing loud... you will want those true, honed Bank 1 tones.

Sorry this is so long, but believe me... I'm a tone nazi just like any other guitarist, but I like convenience too, and so I like Line 6, and I'm here to say Line 6 can get you 90%-95% of what you want from "the real thing", however, it's the real thing you can dial in a matter of minutes... I'm confident this is not the case with Line 6.  You can get it there but it really takes time.  The good news is, if you spend the time, you get an amazing programmed tone and you won't mess with it again... or you might try out of curiosity, but largely you won't change it (or at least this has been my experience).

Hope this helps... the message should read: Take your time and dial it in for live sound (if you play live) and whatever you do... don't understimate the investment you have to make for a Line 6 tone.  That's the trade off.