The loss of Wilson during Chuck's escape from the island. It says a lot about Robert Zemeckis' directing skill and Tom Hanks' acting skill that this movie can make you cry over the loss of a volleyball.
The revelation that Chuck had contemplated suicide while on the island - and circumstances conspired to prevent even this.
Chuck's monologue to Stan.... " And now, here I am. I'm back. In Memphis, talking to you. I have ice in my glass... And I've lost her all over again!"
The scene when Chuck and Kelly meet again...and she reveals she's gotten married and started a family.
"I knew. I knew you were alive, but everyone kept sayin', I had to stop loving you. I had to let you go."