With respect, I disagree. First, you asked for Reagan's biggest mistake, not Bush I; each was egregious. Second, Kennedy has done much, much more damage than Souter. While both have been on the wrong side of major decisions, it is often Kennedy who writes the decision - the "sweet mysteries of life" pablum from Casey, for example.
SoutOr was such a complete MISS by H.W.Bush I suspect even Obama couldn't pick someone more to the extreme left.. Kennedy ws a crap shoot after the Borking"