I have done it from NY Penn station twice to WDW and once to West Palm Beach. (Have also done the Autotrain). It is a long trip so be prepared.
I would definitely do it again (we are actually booked on the autotrain for April), I just wish the restrooms were cleaner or should I say cleaned during the trip, lol.
As long as you know what to expect, you will be fine. Expect delays (we only had a delay for one trip). You can bring a dvd player, cards, pillow and a blanket, it gets cold, etc. You can bring snacks, drink, food, etc. for part of your trip. The food in the dining car is pretty good - the counter - well everyone has a different opinion -
Also arrange for a car to pick you up once you arrive.