Ah, so many great memories! Hands down, my favorite Con guest of all time was Wil Wheaton. He came to DragonCon in 2012, and told a story about meeting William Shatner that literally made me laugh until I cried.
One of the funniest moments I ever remember is when Christopher Judge came to DragonCon and learned about Furries -
The Mythbusters two years ago, agreeing to use a terminally ill cancer kid's ashes in an experiment. It was his Make-a-Wish and was a great segway to conversions about space travel & the afterlife, etc.
No one gives better panel than John Barrowman. Also, I never miss the "An hour with Jim Butcher" panel - he's my favorite author, so I'm biased - but his panels are always super funny and a great insight and tease into his books and writing process.
That does remind me - I always attend a panel for Sherrilyn Kenyon. I look for the panel where it is just her, instead of with several other authors.
Warehouse 13 had a phenomenal panel after they learned they were cancelled, they told secrets and leaked footage. They said, "what are they gonna do, fire us?" The lead actors cried and gave out hugs, etc.
My two favorite panels were last year. Sylvester McCoy had a bum leg and was riding all over the room on a scooter, going right up to guests taking their questions and just being silly in general.