The directions the receptionist gives the Griswolds to their rooms are accurate for the Mirage Casino.
The living room in which Wayne Newton and Ellen have dinner is at Wayne's real-life Las Vegas home. When his house was on MTV's Cribs (2000), the same room was featured.
Clark tells Rusty and Audrey that he hardly recognizes them anymore. It's a reference to the fact that different actors have played the Griswold kids in each of the "Vacation" movies.
The house in Vegas Vacation is the same house featured in National Lampoon's Christmas Vacation. When Clark pulls into the driveway, you can see the neighbour's house still has the same second floor window, the one Clark had ruined when hanging Christmas lights.
Ellen Griswold's full name, "Ellen Priscilla Ruth Smith Griswold," is actually a tribute to actress Beverly D'Angelo's mother, whose maiden name was Priscilla Ruth Smith.