I set audio to ‘Rbpi On-Board Audio’ and then ran amixer cset numid=3 2 and it seems to survive reboots. Latency seems pretty low for me. SetBFree is very playable. As far as I know the HDMI on the pi uses the same audio bitstream as I2S, but the DAC will vary from screen to screen.
Display is set to Generic HDMI the following custom config
dtparam=audio=on
max_usb_current=1
hdmi_group=2
hdmi_mode=87
hdmi_cvt 800 480 60 6 0 0 0
It looks like it should work with the waveshare 5 + usb but I don’t get any audio with it. (screen config is fine though)
Edit: this screen https://www.amazon.co.uk/Jun_Electronic-Raspberry-Capacitive-Screen-Monitor/dp/B07PKPMNZP
The hand in that photo must be teeny tiny!
Edit2: sound sample to sate the monocle. MDA ePiano.