We went last year and stayed in Cairo before and after a Nile cruise. Both times we stayed near Tahrir Square as that seemed to be where most of the hotels are. I don't remember seeing many hotels around Khan Al-Khalili, tho it was easy for us to get there from where we were staying. We travelled independently the whole time we were in Cairo, tho we used guides for visiting the Giza pyramids and Saqqara pyramids, and we didn't have any issues. The metro is good and ubers are extremely inexpensive so it's easy to get around on your own. Zamalek is also a nice neighbourhood tho definitely more upscale (it's also where all the embassies are).