No political party should ever seek a conflict which will require it to fight on two fronts.
We all remember what a close thing the battle to defeat amnesty was, don't we? What made the fight so difficult was the fact that not only did the congressional leadership favor amnesty but the president was behind the measure as well. The Republicans who made up the only force opposing amnesty were hampered in their efforts by the fact that their own president kept trying to slip a knife in their backs.
If the Republican Party chooses John McCain as its presidential candidate and if the Party is unfortunate enough to actually win the general election with McCain at the head of the ticket (unlikely, but still possible) Republicans in congress will find themselves spending the next four years (or maybe even eight years) fighting a vicious two front war as they constantly fight off attacks from both the Democrats in congress and the White House.