I use 1Password and 2 Yubikey.

Both yubikeys are configured to enter the same impossible to memorize password on a press to unlock 1Password, hid mode is supported by every device with a USB ports.

I also use them as an otp second factor when a site requires it.

Finally, they are configured with a x509 certificate that I use as my ssh keys. I generate one key per devices that way the secret never leaves it and I require a pin to unlock the key. For convenience, I use an ssh agent to cache the pin

I could also use them for pgp signature and encryption but I have no use case for that.