When that insane gremlin has Billy sitting in a dentist chair and is attacking him with the dentist tool, at some point he asks, "Is it safe?", for many it must have seemed senseless, but it is actually a nod to the 1976 movie "Marathon man", in which, during a scene, Dustin Hoffman is sitting on a dentist chair while tortured with a dentist tool by an ex- Nazi (played majestically by Sir Lawrence Olivier) who keeps asking him the same question once and again.
The opening shot of Manhattan is the very same one used in Superman IV.
Director Joe Dante, who made the original, didn't originally want to make a sequel, as he felt the first film was a proper self-contained story. Thus the studio decided to move on without him. However, after failing to find an adequate replacement director and being unable to find a satisfactory script, they again approached Dante. Dante agreed to do the sequel if he was given complete artistic freedom, which the studio granted given the success of the first film. Dante decided that since he didn't feel a sequel was necessary, he would base the entire film around this fact, by making the sequel something of a satirical, farcical parody that made light of the original film and the concept of making a sequel. (Hence the abundant absurd content and numerous meta fourth-wall-breaking jokes).
According to director Joe Dante, the humorous "End of the World" broadcast that Clamp Cable Network has on stand-by is based on reality. Dante discovered that at least one major news network (allegedly under order or suggestion of media-mogul Ted Turner) has a similar video on standby in the event of a world-ending catastrophe. Dante and the other filmmakers found the concept so darkly humorous, it was incorporated into the script.
Director Joe Dante had previously directed the original "The Howling", but passed on directing the sequels. Co-star Christopher Lee had coincidentally starred in the first sequel "Howling II." Upon being cast in this film, the first thing Lee did was apologize to Dante for his involvement in the "Howling" sequel, as it was generally considered an exceedingly poor sequel that tarnished the legacy of the well-received original.