Earlier quoted context omitted.
I think devy means that you usually cannot add a U2F as the only second factor - you usually need to first add TOTP or phone number as backup. So, an attacker can just target the weaker factor and ignore U2F. I certainly had the same thought.
The prime thing U2F mitigates is phishing attacks. You literally cannot be phished with U2F, you try to auth against the wrong domain and you get a different secret - so they can't then pass that on the backend (i.e. the real site) and login as you. Sure your TOTP might remain, but you're not using it, so it's not liable to be taken.
"Literally cannot get phished" is woefully far away, because the phishing-resistant property of U2F has a giant hole in the side of it (fallback factors) and therefore still relies on human vigilance.
I do use U2F though, because it is pretty convenient.