Maybe my social circle is just abnormally uninterested in retro gaming, but I've always wondered how people in this hobby--most of them adults in their 30s, 40s, and 50s--justify to themselves the decision to go 4 player instead of 1 or 2 player when designing and building a MAME cabinet. That is to ask, how often does one really have 4 people in their home at the same time who actually want to play the same 25+ year-old video game? I host parties semi-regularly and I suppose, if I really wanted to put such a machine to use, I could cajole 3 guests into playing Trog or TMNT with me for 10 minutes before they got bored and walked away to go socialize with the other adults. The problem is, my enjoyment level when playing seems to revert to the lowest common denominator of the other participants; it's just not very fun unless they share my enthusiasm for the experience.
When I was dreaming up my cabinet build I had idealized visions of it being the centerpiece of social gatherings at my house, with friends and family huddled around the machine, clamoring for a chance to play and compete so that we could all revel in retro gaming goodness together. In real life, it turns out that being a big fan of old video games is a quirky and rare disposition for a man my age to have. Hardly anybody else has taken more than a fleeting interest in playing on the machine, and over the years the hobby has morphed into one of glorious solitude for me, where the absolute maximum enjoyment I get from it is when I'm down in the basement by myself, often late at night, with a cold beer, hammering away at getting a new high score on a classic game like Donkey Kong or R-Type. And you know what? I love it that way, and wouldn't change it even if I could.
I guess I'm rambling a bit. To the OP, if you think it will get used and the 4-player games are that important to you, then go for it. Alternately, you could just do a 2-player layout and keep some USB controllers on hand for cases when you have 3-4 people eager to play the same game at the same time. That's what I did, and in 6 years of having an up and running cabinet, I've plugged in a USB controller exactly once.
I would like to point out that multi-player track-ball games have been the most successful at generating interest in crowds--Golden Tee, Shuffleshot, World Class Bowling, etc.