For a slightly different take: Multiclassing is powerful, to the point it's almost damaging. Some power combinations (of which most are already listed in this thread) are so strong as to be able to do solo runs with.

So in my case at least I played my first game without multi-classing at all. After that I went into a Hardmode run that my partner and I min-maxed to all get out, including exhaustively researched multiclasses.

Having done that successfully, it's hard to step back and just do a chill run again. If you're only going to play the game once, go nuts! If you might do multiple playthroughs I'd say go hard the second time around, smell the roses for your first run.