Winning the presidency or the senate, the only two things the average voter seem to actually care about, would be very difficult to win as a third party.
Local government though?
Those can definitely be done. You won't strike straight at the top right away, but you can start building smaller parties at smaller levels and grow them from there.
But no one wants to even try that. I do agree that our system makes it harder to achieve party plurality than the parlimentary system but that doesn't mean we can't at least try. These two parties are strangling the life out of this country.