Man in the middle attacks of course, which are possible on insecure connections. With the prevalence of root certificates installed on people's computers as a corporate policy, by shitty anti-viruses, etc, it's very much possible to compromise HTTPS connections.
The TOTP 2FA code acts as a temporary password that's only available for a couple of seconds. A "one time password" if you will.
Yes, it still strengthens security.
Read 1Password's article about it: https://blog.agilebits.com/2015/01/26/totp-for-1password-use...