I built a 4-player cabinet for my kids (and me). It's the only Christmas present they're still playing with.
I have noticed though that when they play 3 and 4 player games there is some keyboard combination they're pressing that gets them back into windows. The game is still running in the background. You just can't get back to it. Fortunately, I extended the PCs power button to the side of the cabinet with an arcade button. So, they just press the button and XP does an orderly shutdown. Then another press and it comes back up in the MameWAH interface. Still, that sucks when you're playing a game and you have to start over.
As such, I've remapped all the keys so there are no conflicts. Player 3 stick controls used to bump into player 2 buttons. Not that the 2 would ever be used at the same time in a game, but that doesn't stop people from hitting them by accident! Anyway, I also removed the use of all the "system" keys: CTRL, ATL, SHIFT, etc. Every control on my panel has a unique non-system key associated with it. I did leave ESC mapped to my "EXIT" key, "ENTER" mapped to my "SELECT" key and TAB mapped to my "MENU" key, but those buttons are across the top of my panel and out of harms way.
After the remapping I entered the Mame menu and the "general controls" section after that. I've reset all the controls to match their new mappings.
Does anyone see a downside to this?