The only way I think 2FA makes sense in this context is by using multisig. TOTP/HOTP is useless for wallet security, as you might as well just store a 2nd key instead of a TOTP/HOTP token and eliminate the need for a trusted third party verifying your OTP.
I'm very much in favor of making things like multisig, paper wallets/cold storage, and offline signing easy and accessible through the UIs in order to give each user strong personal control more easily. I'm against any system that puts the community in the position of taking shares from a supposed thief and transferring them to a supposed rightful owner, or allowing payer initiated chargebacks. Such things invite more fraud than they prevent, and the new fraud is more arbitrary and less preventable than the previous. Just look at the forum exchange scams relying on Paypal. If I lose my shares or have them stolen, I want it to be because I was lazy or careless and didn't maintain control of my keys properly, not because a weakness designed into the system motivated a con artist to paint me as a thief so he could play the victim.