I've been gigging mine for a year. Stock speaker. Mostly use the Crunch channel with gain about 12-1:00 and Blues set for clean-ish with some dirt as I dig in. I also use an Analogman King of Tone to boost either side for additional shades of gain. I use this setup for a cover band that plays...
I have the 5:25+ and had the same experience when I bought it new (but sitting in the shop for over a year!) I swapped preamp tubes one by one with a brand new Tung-Sol until the noise went away. I don't remember which tube it was, though. I had a similar problem I noticed this past weekend...
Old thread, but I just bought a 5:25+ yesterday and got back on this board after a long time, having sold my Lonestar Classic years ago.
I haven't put a neo in a MESA before, but I put 2 neo Lil-Texas speakers in my 1966 Pro Reverb. They sound great. I use Texas Heat speakers in a Blues Junior...