There's just less space, so it's harder to get things in and out. And you have a smaller cooler because there's less space, at least for air cooling.
I haven't used itx with video cards, but that's hugely constrained...
They were obsolete a decade ago, but priced out by artificially expensive "SFF PC" cases, fans, and power supplies. PC building completely transitioned to fashionable cargo cult in the late 2010's, with the rise of twitch.