Hillary has shown already that she is not a great campaigner. By all rights Obama stole the nomination from her in 2008 by out maneuvering her, and having a better strategy. I have heard that she is approaching 2016 differently than 2008, but we'll see. I think the Republican's best shot would be to run Christie with a Southerner on the ticket. that would be winnable.
Some people in liberal circles are already talking up Sen Elizabeth Warren, but I think she is probably too liberal to sell herself to the suburbs of major cities, Ohio and Northern Virginia where a Dem has to win to get elected.
Don't forget the electoral map now favors the democrats, and if Hillary runs a better campaign than she did in '08 she still has to be the favorite in the race.