Sega Megadrives managed easily 6-8 button (Street Fighter 2 standard).
The most notable differences with other consoles using the Atari spec specs is with Sega systems (Master System and Megadrive)as the Atari standard became Sega standard (most sold console using this standard).Yet simple re-cabling can be achieved thanks to get a proper adapter made simply :
* a pair of "Atari / 9 pin serial" connectors (one male and one female)
*and simply rewire between both as fit.
This allows to keep the original configuration of Sega compatible Pads/joysticks and benefit from the higher quality level from them.
A clever move may be to put such converter as a box with wires easily removable/changeable (not soldered, but inserted thank to proper solutions).
This would allows to configure more easily different configuration configurations depending on the Game controllers you may find.
*Sega Master system or MegaDrive/Genesis
*Mais even be suitable with Seag Sega LightGuns or Atari/Amiga mouses if you can find a proper Power sourceand perhaps cables with a bit of electronic composents integrated (diodes, resistors ?). As a result it may be a problem to find proper Joysticks for your PLUS/GX4000 with benefit from 2nd button, as Sega models won't often fit entirely but are often of a better quality/availability.
As a result is may be a problem to find proper Joysticks for your PLUS/GX4000 with benefit from 2nd Megadrive paddles use Start button, as Sega models won' t often fit Amstrad fire1 and are often of a better quality/availabilityButton 1 as Amstrad Button 2.
Other noable differences are compaired to Atari ST as the mouse can't fit unless powered.