How many play throughs would it take to get all achievements?
Solution 1:
Once you complete a part of the story, at any time, you can go back and hop around to get the various achievements. The problem is: What do you define as a 'playthrough'? If you are looking to estimate the time it would take, due to the random nature of dungeon and event generation and positioning, this is a flawed metric.
If you consider a base definition of a playthrough as playing from the start of act 1 to the end of act 4 sequentially, not accounting for re-instancing the areas to farm dungeons, drops and events, the absolute minimum would be 4 runs for each of the 10 characters on each difficulty, assuming everything worked out perfectly and you found all the random stuff and all your characters leveled to 60, making for a total of 40 playthroughs, with at least 4 of these being hardcore on each of the difficulties and at least 5 of these being multiplayer, playing each class at least once and each difficulty at least once.
Solution 2:
The 40 play through's is almost right but you forget the achievement for each class that require you to level 2 characters of the same class to level 60. That will add quite a few more play through.