USB stack uses a lot of CPU, a lot hardware is missing and is software emulated. Some USB 1.1 keyboards do not work at all (2.0 are fine).
Constant issues with power hungry peripherals. Unstable USB connections. WiFi has tiny antenna and is prone to interference...
Software "support" is limited to some strange Debian version. Video playback acceleration works, but good luck dealing with outdated packages. I tried to use Pi for router, and included NetworkManager could not even handle WPA2 (only WPA1). No hardware acceleration for encryption, goodbye disk encryption or SSH...
And it is bloody expensive, for 160 euro (4GB, PI 4), I can get much better x86 mini computer, that runs any mainstream distro, has way more stable hardware, and comparable power consumption. Pi 4 B has Broadcom BCM2711 CPU that is 28 nm...