Something that occurs and is later ignored and/or later negated by the general population and is considered to "never have happened." This is usually in reference to a specific movie or game within a franchise, but can sometimes refer to an event or relationship.
Tom: Have you seen the new Terminator series?
Bill: Yeah, it totally negates the third movie, giving it the Highlander 2 Effect. But I can live with that.
Tom: They made a third movie?
John: You and Karen were pretty drunk last night. I knew you were friends, but I wasn't expecting the two of you to go home together.
Brad: I already called and talked to her. We agreed that last night is coming under the Highlander 2 Effect, so we can stay friends without all the weirdness.
John: It's cool. Then as far as I'm concerned, you just crashed on the couch.