Who/What bare the most responsibility for the loss of Hillary Clinton?

[TML]

Hillary herself was the main culprit.

Her campaign was considered out-of-touch with significant segments of the general public.

Yes, external factors (e.g. Comey, Russia, Fake News, Sexism, etc.) were also involved, but if she had run a stronger campaign to begin with (i.e. additional outreach to working class voters, especially in the Rust Belt), those factors wouldn't have been enough to tip the election the other way.