We all know that Nintendo rejecting Sony CD-ROM Drive kinda mistakes but lets get specific?
I'd actually go a little more general than that and suggest Nintendo's handling of that entire SNES CD. Everything they did about that add-on was a shit parade. The "betrayalton" of Sony that led to the birth of the entire Playstation brand is the obvious one, but there's also their eventual scrapping of the project. So they burned bridges with Sony to go with Philips, then they burned bridges with
them, and also agreed to let Philips release Hotel Mario and the godawful Zelda games, after years of Nintendo being extremely anal about keeping their reputation of unwavering high quality. Dropping SNES CD also forced many titles to be canceled or get severely downsized, like Secret of Mana (its original vision sounded so much better than what we ended up getting), and at the end of the day the damn thing wasn't even released.
So in short, the whole debacle:
-Singlehandedly created their best/worst competitor
-Spawned a second awful console
-Directly led to the creation of some of the worst games of all time to use Nintendo IPs
-Eviscerated the original vision of many games in development
-Screwed over two companies
-Wasn't even released.
Nice going, Nintendo. Couldn't have possibly gone any worse.