If you mean a trip from Karachi, then 2 nights 3 days trip is ideal for Tharparkar, especially after the rains this year.
DAY 1: Start your journey early, like 5AM, have breakfast at Gharo--Cafe Imran (about 1-1:15 hours)
From there, take a short tea break at Badin or Golarchi (approx 2 hours). Then drive straight to Mithi (approx 1:45min) or Islamkot (2:15min). Have a short break at the bypass, and then drive towards Nagarparkar (1:30min). Rooplo Kohli motel is a great place to stay. In the afternoon, you can visit Jain Temple, and Bodhesar mosque or visit Qasbo village.
DAY2: You can start at your own pace, and if you hadn't explored Nangarparkar fully on Day 1, check out the surroundings/sites on day 2, and then in the afternoon, leave for Gori Temple enroute to Islamkot and Engro Coal Mines visit. I don't know if they (Coal Mines) allow tourists or not, but you can arrange a visit if you know someone there. A good place to stay in Islamkot is the container city hotel (SZS Facilitation Centre), OR you can drive 30-40min more and stay the night at Mithi which has got multiple guest houses. You can plan your day in a way so that you may be able to visit Gadi Bhit in Mithi and see the sunset. It's an elevated area from where you can see whole of Mithi and surroundings.
DAY3: Experience sunrise at Gadi Bhit, If you hadn't done the sunset part the day before and start your journey back at your own pace. However, you can have an option to visit Umerkot (approx 2 hours drive from Islamkot) and come back to Karachi from there by exploring a new route i.e via Mirpurkhas, Hyderabad. For that your best bet is to stay the 2nd night at Islamkot and got to Umerkot from there.
You can reverse the order of the trip if you like, such as:
Day 1: Karachi-Umerkot-Nagarparkar via Hyderabad and Mirpurkhas
Day 2: Nagarparkar-Islamkot/Mithi
Day 3: Islamkot/Mithi-Karachi via Badin and Sajawal
