A quick Google search shows that a number of commentators (including Andrew Sullivan and Dahlia Lithwick) have already compared presumptive Republican vice presidential candidate Sarah Palin to withdrawn Bush Supreme Court appointee Harriet Miers.
To be sure, there are parallels, including criticism of both by David Frum (here and here) and Ramesh Ponnuru (here and here). But there’s a big political difference too: Miers infuriated the conservative Republican base, while Palin, if she appeals to any constituency in the party, appeals most to conservatives.
But suppose that because of the “heartbeat away” concerns, there is an outcry to replace Palin on the ticket. Could Sen McCain do so if he wanted to? Of course, if it happens before the convention vote, there would be no issue. But even after the convention, as far as the Republican rules go, the power to replace is right in the hands of the RNC, which surely would bow to a McCain replacement decision. Rule 9 provides:

Filling Vacancies in Nominations
(a) The Republican National Committee is hereby authorized and empowered to fill any and all vacancies which may occur by reason of death, declination, or otherwise of the Republican candidate for President of the United States or the Republican candidate for Vice President of the United States, as nominated by the national convention, or the Republican National Committee may reconvene the national convention for the purpose of filling any such vacancies.
(b) In voting under this rule, the Republican National Committee members representing any state shall be entitled to cast the same number of votes as said state was entitled to cast at the national convention.
(c) In the event that the members of the Republican National Committee from any state shall not be in agreement in the casting of votes hereunder, the votes of such state shall be divided equally, including fractional votes among the members of the Republican National Committee present or voting by proxy.
(d) No candidate shall be chosen to fill any such vacancy except upon receiving a majority of the votes entitled to be cast in the election.

Depending upon when such a replacement would occur, there could be state law issues. In Texas, for example (which has other problems right now with Democratic and Republican presidential candidate names on the ballot), any withdrawal of a candidate in fewer than 74 days before the election (we are currently 67 days before the election) results in the withdrawn candidate’s name remaining on the ballot.