To cheatfreak47 and to all the other forummers who mentioned this, yes, I'm updating the default region for US+Europe games to NTSC in the next release. And there will be override to force it to run in Default/Force 60FPS/Force 50FPS. Apologies for that, since Sega was never my thing and I never knew Sega ROMs had multi-regions.
To do that I simply had to set some settings within PicoDrive to always put the US region as priority.
Yes, unfortunately.

To ensure that all games ran at 60FPS, it was intentional that I lowered the sampling rate for Old 3DSes so that I could move the FM synthesized music into the 2nd core (which was not fast enough to generate FM synthesized music at the full 44.1Khz). You can try to enable the low pass filter - that will at least help to make everything sound closer to the original hardware (a little muffled like our old TVs did last time). But if either is not acceptable, you'll probably have to stay with Retroarch for now.
I don't know if I have a solution for this but... it may stay this way for a while.
I also realized PicoDrive has no native support for cheats, so cheat support is going to have to come a little later than just this week.

Oh btw, instead or merging your PR, I manually updated those codes into my main branch. FYI.
That should be up and coming in a patch by end of the week.

Thanks for waiting!
The 6 button thingy and the sound lag should be ready in a quick patch by end of the week.

Thanks for waiting!