Glad someone has the ambition to do more than transit Pakistan.
I first discovered this country as a backpacker in 2003 and totally fell in love.
In 2007 I came back with my own car; I liked it there so much that I stopped, did some volunteer work and over the next two years spent one year (over three visits) in Pakistan, exploring every part of the country.
At this time the escorts were not as bad as they are now, but I also got around them by having a local-looking truck and dressing locally.
I actually lived in Sindh and can tell you that it is full of interesting sites; not the mind-bending scenery of the north, but a lot of Sufi shrines, festivals, some of the most ancient archaeological sites in Asia, Hindu temples and ashrams and a lot of extremely friendly and laid back people.
Anyway, to get to my point; travellers always end up in Quetta (probably my favourite city in Pakistan, though I doubt they'll let you do much there these days) and then go down the pass towards Sukkur. But there is a perfectly good highway south from Quetta which goes down the fringes of the Suleiman and Kirthar Mountains, dropping to the coast (and passing the turning to the fantastic Makran Coastal Highway - a spectacular side-trip but probably also out of bounds if the police see you're a foreigner) and into Karachi.
As one of the world's largest cities Karachi seems to be totally overlooked by visitors, which is a shame, as it is Pakistan's real metropolis and most important city. It's not a place with many specific sights (as big cities in the sub-continent rarely are), but if you really want to understand Pakistan, I think you have to spend a bit of time here. It's also logical to start here and drive up the Indus, the very spine of the country.
This makes me wonder; I'm pretty sure you can lose your escort in Karachi, and then make your way up the National Highway at your own pace. The police there will never see foreigners and you may not be stopped at all. Then you can stop in Hyderabad (where I used to live), explore the desert a bit, go to the shrines at Bhit Shah and Sehwan, check out Ranikot Fort and Moenjodaro and any number of other little things you run into on the way. Back in the 1980s and early 90s this region was quite lawless, and out of date travel guides (i.e. all of them) will probably still tell you that Sindh is dangerous, but this is total crap. Outside of Karachi (which has plenty of crime, like all big cities) I reckon it's the safest part of the country.
Here are a couple of my articles (mostly) about Sindh:
https://eurasiaoverland.com/2008/02/15/7ii/
https://eurasiaoverland.com/2009/09/10/15/
In years of travelling around Eurasia, Pakistan is definitely still my favourite country. Don't turn it into a transit of Punjab to the Indian border.
EO