The "they don't close Florida" line might qualify in light of the recent immigration incidents.
Post-recession, it's rather harder to laugh at Eddie's money troubles.
Hilarious in Hindsight: Clark's line about how he'll wake up one day to find the kids are grown up is quite prophetic. Over three more films and fifteen years, the kids kept getting recast to stay roughly the same age, but then suddenly we get an adult Rusty going on his own vacation in the 2015 film.
Incest Yay Shipping: Dana Barron and Anthony Michael Hall as Audrey and Russ seem closer than a normal set of siblings would be, which led to speculation they had a offscreen relationship.
Nausea Fuel: The family at one point stop off at a picnic area to have some lunch. As they're eating the sandwiches they notice they're soggy, And then it hit them that Aunt Edna's dog urinated on the food. The family is understandably disgusted but Edna just shrugs and continues eating. Ugh.
Sequelitis: With a different director, no creative input from Harold Ramis or Chevy Chase, completely different characterization for Russ & Audrey, and some of the better gags being telegraphed too far in advance, European Vacation is nowhere near as beloved as its predecessor or its follow-up Christmas Vacation.
The 2015 sequel/reboot is getting this reaction too with people who dislike the heavier amounts of crude humor in comparison to the original, and how the film is essentially just a kinda-sorta remake of the original (with one of the film's own trailers lampshading this fact) with much more heavy-handed attempts at comedy; highlighted further by the fact the 2015 movie recreates almost shot for shot the famous "flirting with a hot woman on the highway" scene, only this one has her die violently in a head-on collision, making many viewers say "Dude, Not Funny!"
Values Dissonance: The whole sequence in the black neighborhood was pushing things even at the time, and comes off as horrendously racist now (though it's actually toned down from the equivalent scene in the original short story).
What an Idiot: The whole mess of a vacation would have been avoided had Clark (or even the far more rational Ellen) made a simple phone call to Wally World to confirm it was open for the season; they would have learned it was "closed for repairs." (Then again, phone call equals no movie and no fun for us, the viewer.)
Unless whatever happened to make Wally World need the repairs took place after the Griswolds departed or Clark decided to drive them somewhere else.