This is probably going to sound weird to a lot of people because everyone seems to like this amp, but when I first got my Friedman Twin Sister, I was super disappointed.
I was playing a Smallbox, so I was used to more mids, quicker attack, and a sharper, faster sound. By comparison, the Twin Sister sounded slower and very scooped, with a huge boomy low end and a bright toppy treble. I was so disappointed, I immediately bought a BE-100 Deluxe off Craigslist (which I love) and figured I'd sell the Twin Sister.
But over the few weeks I had it up for sale, I kept plugging into the Twin Sister here and there just to make sure I wasn't missing something. I spent time tweaking some settings. I lowered the "Deep" to 10:00-ish to tame the boomy low end and reduced the Bass on each channel to the same. I pushed the mids harder, up to about 2:00-ish, and kept the treble in check around 12:00-1:00. Then I played with the gain and structure switches. Ultimately set one channel up to be a little cleaner (medium gain saturation, gain around 12:00) with no bright switch and the other channel more aggressive (high gain saturation, gain around 2:00) with the bright switch engaged.
I started to really like it, especially with my lower output guitars. I discovered that the extended bass and treble really worked for my guitars with softer Alnico 2, 3, and 4 pickups. Those frequencies in the amp really made up for the frequencies lacking in those pickups. I also discovered it takes boosts super well -- even better than the Smallbox -- and I found I could get a whole range of sounds out of it. It also sounds great with single coils, especially if you add my Xotic "Super Sweet" booster in front of it with the gain knob on that pedal around 8:00-9:00. Next thing I know, I'm plugging into it more than my Smallbox.
Well, the Twin Sister finally sold. A guy paid me just $100 short of what I paid for it new. It was a great deal for me and I had a ton of cash in hand, but immediately regretted it. I had really grown to love that little amp.
The next day I'm walking through one of my local boutique music stores here in SoCal and boom there is a Twin Sister sitting out on display. I couldn't believe my eyes. (It was not my same amp.) I didn't even play it -- I immediately bought it. Now it's back on my amp rack and is one of my favorite amps!