Griffin Dunne was born into a cultural family. His father was a playwright and I think that his background has a lot of similarities with Scorsese's favorite, De Niro. Maybe that's why he is so good in this because he looks like such an ordinary guy. He is slightly more handsome than De Niro but in a crowd he would totally melt in.
The film was not one that Scorsese had decided to film himself from an early stage but I think that without him it could have been a terrible bore. Scorsese has a rapport with actors that is totally unique. That's why so many of the actors in the movie give the best performances of their career here. Let me name just a few:
1) Rosanna Arquette: This and her performance in Desperately Seeking Susan go hand in hand here. She has been kind of lost since then but the way she plays totally clueless and still manipulative is really superb. It also helps that she is extremely hot. 2) Catherine O'Hara: Her insanity is set in stone almost from the first time we hear her speak. It's odd that she has been mostly known as a comedienne. 3) Teri Garr: Another comedienne. Sidesplittingly funny in Young Frankenstein and here demonstrates an untapped range which has gone unused to this day. 4) John Heard: His sinister personality is not apparent but you can almost feel that he is about to burst into a fit at any moment. It's also funny to think that five years later, he and O'Hara would play the most loving parents to a boy who would be the biggest box office draw in the early part of the 90's.
There are also a few cameos from actors who were primarily known in underground movies where Scorsese started his career and even a few seconds with Cheech and Chong.
So I will say that had Scorsese not made so many other memorable films this would have been his crowning achievement. It does have a few moments where it goes a little over the top, like when we meet the character Horst, played by perennial weirdo Will Patton, but those scenes are such a small part of the whole that it can be overlooked. For the most part it's a fascinating experience and one that can never be duplicated.