My biggest issue in my design process is separation between 2 players.
I used to stress over that as well, but it dawned on me one day that it really wasn't as big a deal as I thought it was.
Some cabinets have the players pretty close to each other (The "Z backs" used with SFII comes to mind, but I'm sure there's others) where you're basically bumping each other in the elbows. Then you have your cabs with player settings so far apart, you can park a wheel chair in there, like Gauntlet. On the MAME scene, some people pack two players into the width of a centipede while others spread them out so far apart, you can theoretically land a Cessna on their CP (#4 and especially #11 at CrapMAME are really good examples of excess distance). It boils down to preference.
Think about a two player cabinet you really liked in the arcades, then get the dimensions and derive your new CP from those dimensions. Don't stress. If, even after the cardboard mockup, you construct your CP, you ultimately find you don't like the layout. Pull the top off and start over. Every CP I put together has a top that can be removed (with more or less work) and replaced.
2nd biggest is making sure the CP is big enough to support the players hands.
My current CP project is only 14" wide. I originally had it designed to be 12", but I realized (after a sketchup session) the inset prevents any management buttons, I pushed it to 14". I have a "lazy" stick hand where I rest my wrist on the panel, but I have an "active" button hand where it floats (unless I'm in a long game then it goes lazy). Therefor, I tend to have more space around the stick and less around the buttons. When it comes to supporting players hands, I prefer depth over width.