It depends if you want to gain volume and strength or if you just want to tone up and keep fit or loose weight.
To gain on volume, I would advise splitting your routine in two (upper vs lower body) and work out 4 times a week.
To shape up or just keep fit, I think whole body is good enough. This is less intense for your muscles and allows you to maintain a good health, alternating cardio and weights.
To loose weight, cardio, cardio and more cardio. Running can be quite challenging at first if you have a lot of weight to loose, but other options like kettlebell workouts burn a lot of calories, work your core muscles and are easy to fit in your heavy schedule after a day at work.
So yes, it really depends on your needs, but these are the basics.