So, a question about guitar amplifiers. First, let me say that currently I use a Line 6 Spider III 30 watt, but more often I use a Line 6 Toneport UX2, which is a computer interface, and I use their software called GearBox which simulates amps and effects. Outside of that, I only own a Crybaby Wah and an Ibanez analog delay pedal. Everything else I do with either my amp or my computer. Basically, I want to replace my amp with an amp that meets my specific needs better, and I honestly don’t know a lot about real amps – most my knowledge comes from my Gearbox software and from reading reviews on amplifiers, which after a while kills brain cells.

I am looking for an amp that would meet my needs for both thrash metal/power metal songs and for overdriven instrumental pieces. From my experience with the Gearbox software, a Mesa Boogie Dual Rectifier type amp is simulated, which seems to meet my needs, but Mesa Boogie is out of my price range, even used. For the metal sound I’m trying to get think Megadeth and the overdriven instrumental stuff a tone close to Santana. I know I’m not going to get a tone as good as theirs without spending a LOT of money, but I just want to get closer in that direction than my Line 6 Spider is able to go.

I could get by for my needs with a loud 8” or a 12” single speaker amp, but would really like a 2x12 and my budget is like maybe $500 for this. What amps should I check out?
your best bet for $500 would probably be a peavey valveking, but even then you're a little over.
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Jet City JCA20H - Mesa Rectifier 2x12
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There is no way to recreate those tones out a an 8" speaker. You'll with need atleast a 1x12 combo.

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There is no way to recreate those tones out a an 8" speaker. You'll with need atleast a 1x12 combo.

He says he'd prefer bigger ones so that's not a problem.

But check out what the guy I quoted has, B-52 amps, although I'm not sure on the exact sizes of the amps in terms of speakers/wattage. I've heard it referred to as the poor man's Mesa. My friend, who is really good, uses a B-52. He plays classic rock overdriven stuff mostly, but shreds some too. It has pretty high gain.
The Valveking is affordable, still a bit more than you have a budget for but it could do the job. I'm not sure what a used Peavey JSX combo would go for so long as you don't mind used. New it would be too much money with your budget (about twice as much). I've heard good things about the Bugera 333XL or whatever it is. It's a good size combo and has a lot of features on that would be useful...just never tried one. Not really sure what else may work.
well santana used Mesa/boogie Mark II's I believe, one of the mark amps, not sure. Megadeth uses Marshall's and Engl's. You could probably find a used Carvin X100B (it sounds like a modded marshall type tone to my ears) or maybe a used marshall JVM 410 combo for that budget and get you in the ballpark of those tones. You'd need an overdrive pedal to kick either of those amps into really heavy metal areas though.
My experience with a valveking was that i bought one, then everyone said you would have plenty of gain with an overdrive pedal. Not true for me but i play a little bit heavier than you. So maybe check out a used valveking but keep this advice in mind. Or check out a used bugera. I wish i would have got one myself, i have no first hand experience but i hear they are great, versatile amps. Apparently they can crap out alot but they will hook you up with a new one or fix it. So I'd say check out a used bugera for sure.