The best way to start planning is to see how much time you can give to driving/commuting. If you are driving your own car, and you only have 2 days, the ideal way is to choose any location which is maximum about 8 hours drive from Karachi. In this way, 16 hours will be out of your trip for driving, and another 7-8 hours for sleeping, so you will be left with 24 hours for sight seeing/relaxing including night time hours.
Karachiites usually have 2 areas for such small duration trips other than the local beaches, 1 is the Tharparkar side, and the other is the Balochistan side. If you carefully plan your itinerary, you can leave at 12midnight, or even earlier if you can, on 11th May (Friday), hence you will have the complete day of 12th May, and more than half of 13th May to explore nearby areas of whichever destination you may choose.
Hope this is helpful.
