When, in the main game, would be a good time to get Hearthfire? When I can afford a house? When I'm a Jarl of one of the applicable holds?

Buy it right away, the houses you can build are far better then any you can purchase in the towns in my opinion.... Happy building....

I started a new game expressly because I wanted to build Lakeview Manor before I'd done almost anything in the game. It's working out splendidly. Now at Level 32, I have my Falkreath home, a husband and two kids. Only a couple of days ago I went to Whiterun to tell the Jarl about the dragon that wrecked Helgen. Also at this high level, I've just joined a couple of factions. With a family and now the dragons have just started flying, I'll soon be ready for Dragonborn. However, I do think I should advance the Main Quest a bit.

By all means, get a Hearthfire house built, the sooner the better. Cheap add-on and cheap to build. I don't plan to buy any of the regular houses.