In the analog camp, I'm a fan of the Tech21 amps. I've had a PSA-1 for nearly 20 years, and have owned both Trademark 60 and a Trademark 10. However, I like having presets and internal effects, so I tend toward the...
Digital camp. I started 10 years ago with a Fender Cyber-Deluxe, and about 5 years ago got a Cyber-Twin SE. I've tried the Vox stuff, and on computers have messed with the Waves stuff and Amplitude, but just don't like playing guitar through the computer. The COSM guitar, amp and effects modeling in the Roland GR-55 is excellent, but using a guitar with a hex pickup and 13 pin cable is it's own can of worms. Still, for flexibility and range of tones (and access to synth features), it excels.
But when it comes down to what's a great amp that sounds great live and is minimal hassle, I keep returning to the Cyber-Deluxe. The Cyber-Twin SE is much more powerful, but to the Cyber-Deluxe just sounds better. Over the last 10 years I've tweaked up a set of presets that sound great, and I constantly get great comments on my tone. I've published my presets (which involved some back-door magic using unpublished features in the amp that are only accessible via MIDI system-exclusive), and there are several guitarists who have used them. The presets range from clean to distorted, over several amp models. I've also worked up a system controlling the amp with a Behringer FCB1010 MIDI foot controller, and it gives me a great combination of ease of use and powerful control access. These days you can put this system together for under $500.
There are a ton of options out there. My advice for all of them is to ignore the factory presets (they are generally useless) and look for the gear with a good interface (what good are great features if it's a hassle to access them), and plenty of memory for storing presets. Then spend some time with it.