I inquired about Genesis audio to Ace9921 on youtube. He seemed to know a lot about all the different Genesis revisions, so I asked about his opinions on getting the best sound from the system, pre/sans any modding. He blessed me with this awesome response:
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What you really need to be aware of is the different motherboard revisions in each of these systems. Here's the general rundown:
Genesis Model 1: In North America, there exist 7 different motherboard revisions: VA2, VA3, VA4, VA5, VA6, VA6.8 and VA7. Genesis Model 1s with VA7 motherboards are the ones to avoid; they sound like shit. The sound is distorted, low-quality and very hissy. All the other motherboard revisions sound the same: clear sound, very high bass, zero hissing, no distortion. The Genesis I use for my 10 Minutes of Video Game Music videos is a Genesis Model 1 with a VA3 motherboard.
Little note: any Genesis Model 1 with a VA2 motherboard will have screwed up Mono audio. Instead of the Mono audio output actually being Mono, it's actually just the right sound channel. The left sound channel is never mixed. The same is true with Japanese MegaDrives that have VA0 and VA1 motherboards.
Genesis Model 2: There exist 7 different motherboard revisions in this system as well: VA0, VA1, VA1.8, VA2, VA2.3, VA3 and VA4. Stay as far away as possible from Genesis Model 2s with VA0, VA1 or VA1.8 motherboards, as the sound is just as nasty as a Genesis Model 1 with a VA7 motherboard. The VA2 and VA2.3 motherboards aren't very good either. The sound is clear, but the volume balance is off, and the PSG is so badly out of tune Sega Master System games have heavily distorted sound. The out-of-tune PSG also makes Genesis games that use PSG sound wrong(Thunder Force games in particular). VA3 and VA4 are fine for sound, as they've got a very well-made sound circuit and the volume balance is almost perfect. VA3s have perfect volume balance while VA4s have slightly louder FM Synthesis than normal.
Genesis Model 3: Only 2 motherboard revisions exist: VA1 and VA2. I've never used a VA1 Genesis Model 3, but I can tell you that the sound off a VA2 Genesis Model 3, aside from being Mono only, is very clear. Its bass is rather weak, but the clarity is there. PSG is also slightly louder on the VA2 Genesis Model 3.
Sega CDX: There exists only one motherboard revision of the CDX as far as I know. Its sound is the clearest of all Genesis systems I've ever used, but it's rather weak compared to other Genesis systems. FM Synthesis is also a bit too loud.
Nomad: Again, only one motherboard revision exists to my knowledge. Believe it or not, the bass is actually STRONGER on the Nomad than on pre-VA7 Genesis Model 1s. PSG is just a touch louder than normal.
Here's a little something you might want to know: there exist 2 different types of Yamaha YM2612s(this is the chip responsible for FM Synthesis) on the Genesis: discrete YM2612 and ASIC-based YM2612. If you find a Genesis with no chip marked Yamaha YM2612, the chip is integrated within the big Sega ASIC on the motherboard, denoted Sega 315-xxxx. This list will tell you what YM2612 each model's motherboards contain:
Genesis Model 1: Discrete YM2612 in VA2 - VA6.8 motherboards, ASIC-based YM2612 in VA7 motherboard.
Genesis Model 2: Discrete YM2612 in VA2 and VA2.8 motherboards, ASIC-based YM2612 in all other revisions.
Genesis Model 3: ASIC-based YM2612 on all motherboards.
Sega CDX: ASIC-based YM2612 on all motherboards.
Sega Nomad: ASIC-based YM2612 on all motherboards.
The main difference between the two is that the ASIC-based YM2612 has a higher sampling rate than the discrete YM2612, resulting in clearer sound, but it usually sounds more "computerized," if you know what I mean. The discrete YM2612 also has more quantization noise than the ASIC-based YM2612. Quantization noise is most noticeable when music fades out, as you will hear that the notes last longer on a discrete YM2612 than an ASIC-based YM2612.
My personal recommendation is any Genesis Model 1 with a discrete YM2612. Sound is best on that. If you find a Genesis Model 1 that says HIGH DEFINITION GRAPHICS on the case, you're guaranteed to have a motherboard with a discrete YM2612. If you prefer the sound of an ASIC-based YM2612, get a Genesis Model 2 with a VA3 motherboard or a Nomad(NOTE: A Nomad is VERY expensive. Unless you can get one for cheap, don't bother hunting down a Nomad).
There's an easy way to recognize a VA3 Genesis Model 2. Take a look at this image:
http://img16.imageshack.us/img16/8452/g mother.jpg
If you turn over a Genesis Model 2 and see this short metal plate, then you've got either a VA3 or VA4 motherboard in your Genesis Model 2. This one has a VA4 motherboard, which has 2 holes punched in the metal plate. Genesis Model 2s with a VA3 motherboard have no holes in the metal plate.
The true sound, however, is that of a Genesis/MegaDrive Model 1 with either a VA0, VA1, VA2, VA3, VA4, VA5, VA6 or VA6.8 motherboard. That's why I use a Genesis Model 1 with a VA3 motherboard. TMSS has nothing to do with the sound quality(it was introduced in motherboard revision VA6, FYI) as the sound circuit is exactly the same in all of these motherboard revision. Sega changed the sound circuit on the VA7 motherboard for a really shitty one that results in awful sound.
Before I forget: if you have a Sega CD and use its Stereo audio outputs, it eliminates some of the hissing from Genesis Model 2s with bad sound. It doesn't eliminate all of it, however.
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Oh and don't forget little-scale has some handy comparisons up here as well:
http://milkcrate.com.au/_other/sega_comparisons/