Aside from price, which makes accepting multiple monitors rather compelling(you can get physically big ones for relatively small amounts of money, because of TVs; but if you want resolution the cost goes up fast and things really start to misbehave if you go high enough that DP MST or the like is required to drive the thing), it mostly comes down to how good your windowing system is at tiling and how well applications that expect 'full screen' can handle playing with others.
A good window manager makes carving up a single large monitor into chunks suitably sized for your various programs easy and painless. If you are enduring a less obliging one, it can be a fairly ugly business, actually less pleasant than getting some help from multiple physical displays, which are more widely respected even by poorly behaved programs.
That said, the 'two side by side, giant bezel in the middle' configuration is not my favorite. A larger primary screen, with ancillary screens on one or both sides gives you plenty of room for assorted lesser windows; but also avoids annoying bezels in the center of your field of view.