Definitely Serenity.
If I had to pick four more...
Train Job, since it was written as almost a second pilot. Also, the ending sets the tone for a lot of the series.
Out of Gas, though it would lose a lot without having gone through the rest of the episodes. Still, sets up how the rest of the crew came on board.
Ariel, because it's THE defining episode for River and especially Simon. Also, it sets up a lot for Jayne's character, which is lost by not watching all the episodes.
After that, it's hard to say.
Objects in Space adds a lot to Simon and is River's pivotal episode. It highlights a lot of the characters and how they react to a clear and present danger. On the other hand, while it is a great episode, it really ignores most of the crew beyond Simon and River, and a bit of Kaylee.
War Stories sets up a lot with Wash, Zoe, and Mal, and is led in by Train Job. It's also Wash's pivotal episode. Again though, a lot of it is lost without the preceding episodes, especially the growing friction between Wash and Mal and its resolution.
I think both would be optimal, but I think I'd choose War Stories over Objects in Space.