Earlier quoted context omitted.
I'm going to assume here that we're talking about a subquery here (SELECT * FROM t1 WHERE x NOT IN ( SELECT x FROM t2 )). If you're just talking about a static list, then the basic problem is the amount of data you get back. :-) The biggest problem with NOT IN is that it has very surprising NULL behavior: Due to the way it's defined, if there is any NULL in the joined-on columns, then _all_ rows must pass. If the col…
It's not just the nullability behavior. My experience with several databases is that IN is always (or almost always) executing the subquery then using its results to match the outer predicate. But EXISTS can work the other direction, matching the predicates from the outer query then passing those keys into the exists, allowing use of an FK index on the inner query's table.
Note that these caveats do _not_ apply to IN, only NOT IN.