Career mode for me, and Im still on my first run. I find the contracts and the managing part of the game very interesting, always keeps me busy and forces me to make ships for specific missions or under certain budget.
For example, I made a nice ship to land on Mun, Minmus and return to Kerbin, costs 380K. After a botched mission, I was left with 290K, a crew stranded on Minmus and a rescue contract on the Mun, wich I needed to do to get money. If I was playing sandbox I wouldnt have changed the original prototype, but Career forced me to make a barebones version, (almost no electric charge, no comms, tiny landing gear, budget life support, no lights, ports or extra fuel, no RCS, no fancy solar panels, no heat shields, no autopilot, minimal reaction wheels, etc.).
I wouldnt have had that challenge in Sandbox. Shaving 100K out of a ship that I already thought was balanced.