Bannon: Comey firing was worst mistake in 'modern political history'
It has some pretty strong competition
Nixon installing a tape system.
Saturday Night Massacre (also the most directly comparable to the Comey firing)
"Read my lips, no new taxes!"
John Edwards' affair with Rielle Hunter.
Gary Hart's affair with Donna Rice
Muskie in tears.
McGovern choosing Eagleton, then supporting him "1000 percent"
"Heckuva job, Brownie!"
Dukakis in the tank.
Howard Dean's scream.
Quayle comparing himself to JFK.
Carter's "malaise" speech.
... and probably more I am forgetting.
I'd put the Comey firing up there, above some of the items on that list, but not on the top. Chappaquidick and Nixon's tape system (and overall response to Watergate) have to remain the big two since they kept a Kennedy from being President, and drove a sitting President to resign in shame. If Trump ends up resigning,
I would place the Comey affair somewhere in the same group. If Trump ends up a one-term president, I think the Comey firing would be on a lower level, approximately at the same level of impact as "read my lips" or Carter's "malaise" speech. If Trump gets re-elected and the GOP holds both houses, then L'Affaire Comey turns out to be merely a tempest in a teapot.
A few of those were added by commenters. I don't think I personally would include "Mission Accomplished," since
(1) It was truly what Trump calls "fake news." The banner "Mission Accomplished" referred to the overthrow of Saddam and the defeat of his army, and as such, was completely fair praise for America's effective military services. Bush, of course, inadvertently flying in the face of Colin Powell's advice, was caught by the Pottery Barn rule ("You broke it? You bought it!"), which meant that the REAL mission, the stabilization of Iraq with a friendly regime, eluded him then, eludes us now, and may remain an eternal mission, forever unaccomplished.
(2) Furthermore, "Mission Accomplished" doesn't really meet the criteria for a political mistake, since there were no signiicant consequences. He was soon re-elected. In contrast, "Heckuva job, Brownie" caused him to drop to the lowest approval rating of his presidency to that point.