I am fighting through my first HQ deployment right now. So far, here's what I think I know...
HQ maintains a master list of inventory items. If the inventory at Store A is substantially different than at Store B, your HQ Item table will be that much bigger. This can make finding items trickier. OTOH, if you had cookie cutter stores this HQ feature would be sweet.
If you use global customers, you lose a lot of control at the store level. Whether this is good or bad is up to you. If a global customer comes in and has a new address/phone number, only HQ can make the change.
Adding new stores where lots of new items are required is not simple.
For me, the ability to see and sell inventory from other stores' inventory was paramount. Centralized A/R was also a requirement. For these two reasons alone, HQ seemed the way to go.
From a strictly software POV, HQ is not nearly as polished as Store Ops. Find screens don't remember which fields you prefer to search--every time you start HQ you need to re-check the 'Search in:' fields. This is a little thing but indicative of how MS regards HQ vs. Store Ops. Look at it this way: HQ sales, by definition, could never exceed 50% of Store Ops' sales. In reality, I'd expect that the SO:HQ ratio is closer to 10:1.
Best of luck, Tom