Whiterun. It has a very reasonably priced home with good storage. It is centrally located which makes it convenient to return to. And it has good one stop shopping just outside the door, everything the happy little smith in me could ever desire.
Whiterun, Markarth (the wife lives there) and sometimes Windhelm for the shops which tends to be armor related or general stalls / stores
Since I've installed Hearthfire I realised that Falkreath, Dawnstar are also very useful for smithing materials.
When I was trying to level up in alchemy and was needing materials to make potions I used Morthal a lot. Dawnstar for smithing and Morthal for alchemy.
Depends on the character, where I live and which town is closest. But for selling loot I prefer to go to Windhelm, where you have no less than three general goods traders, a blacksmith, an alchemist and a court wizard.
Oftentimes Whiterun, but usually Riften. Most of the characters are play are part of the Thieves Guild, Honeyside is a nice upgrade from Breezehome, and there are quite a few merchants readily available. The fact that I like Riften and its surroundings aesthetically helps as well. Riften Hold is probably my favourite hold in the game.
I've been in Riften craploads, since I do the thieves guild and don't fast travel I tend to do multiple quests at the same time like Dawnguard and misc quests and the guild side missions. The Rift will probably be the first hold I complete every location and side mission, I don't want to keep going down there on business.
I look for the closest place to offload my gear easily and get back out on the road. It is usually Riften or Whiterun for all the quest reasons people have outlined; most of them start in either of these two. I also end up coming back to Ivarstead more often if I'm in the middle... especially when I, ah, make a property available in one of the quests.