As Newt Gingrich said (at this link) "GOP can't compete if Hillary Clinton is the 2016 nominee". As discussed at the link the only qualifier I can see is that if President Obama leaves the stage with the country in the same mess as G.W. Bush left it then just possibly Clinton might not be elected.
But with the leftist media certainly be 100% behind the Hillary and Bill show then whoever the GOP nominee might be they would have a most difficult time of it.
Apart from that factor the Electoral College map is currently stacked against the GOP. Even if the 2016 nominee wins back Florida/Virginia and Ohio and holds all the "Romney" states they would still have to win one of New Hampshire/Iowa/Colorado or Nevada as well. Such a scenario is possible with a better candidate than Romney who could turnout the base but if the opponent is Clinton is is a very hard row to hoe.
That being said it may, ultimately, be for the best if Clinton runs against yet another GOP establishment candidate. The all but certain loss, perhaps a massive one, would lead to either the final and total rejection of the centrist establishment domination of the GOP and their candidate choice, and the selection of a genuine conservative standard bearer in 2020, or the breakup of the GOP and the establishment of a genuine conservative third party then.
In life we often have to accept what is rather than what we wish things to be like and if Clinton runs then
the grass roots may have the bitter pill of a third straight loss to swallow, but it just may be that the pill leads to the cure of the centrist disease which has afflicted the GOP body politic.