I had traveled a lot by road from Karachi to Islamabad and vice versa.
My analysis say that Indus Highway isn't good at all.
The route from Rawalpindi/Islamabad should as follows:
Islamabad to pindi bhattian via M2
then merge on faisalabad motorway M3
then merge on to gojra motoway M4
then take National Highway N5 towards Bahawalpur via Kabirwala and khanewal (this will bypass multan)
then keep N5 and you will pass from following locations on N5
Ahmed Pur East
Rahim Yar Khan
Sadiqabad
Dharki
Ghotki
Pano Aqil
Naushahro feroz
Moro
Hala
Haiderabad
from haiderabad you will need to take bypass and merge onto Super Highway, Super highway is being reconstructed and and same road will be M9 motorway till Karachi
This is surely the shortest and safest route. You should keep in mind that you should not travel in late hours from sadiqabad to Haiderabad. It is unsafe with family and so on Indus Highway as well. The interior sindh patch from sadiqabad to Haierabad is highly not recommended to be traveled in night time either you using National Highway or Indus Highway