Online access for multiple users is easy to set up, but the program is often slow to respond, even over a good internet connection.
Lacks the Advanced Search of all transactions, regardless of type, that makes QB Desktop so much more flexible and easier to use.
QBO also hides advanced options (delete transaction, undo reconciliation, reverse transaction) behind multiple layers of menus. I understand this to be part of an effort to make the product friendlier to non-bookkeepers, but I use the Accountant version, and these functions are still hidden under layers of GUI. I far prefer the capacity that QB Desktop offers to strip the GUI down to a workspace and a full selection of drop-down menus.
Lacks a real inventory system. For that, you will have to use an outside app, and that is going to raise the cost.
It is also near impossible to create your own solution for missing features, as Intuit has obscured the underlying database mark-up language. For instance, if you are a non-profit that need to apply customer and class tags to multiple transaction lines for later reporting, it is far quicker and easier to do that in a spreadsheet and import the transactions. But you can only DIY that in QuickBooks Desktop and with its publicly accessible IIF mark-up language. If you use QBO, good luck finding (and paying for) a third-party app to fill this need.
I also find that the labeling of transactions (e.g., Expenditure is more prominent than Bill) and the prominence with which the bank integration/transaction matching feature is promoted to conceptually favor cash accounting practices, which are not preferred or even legal for most businesses. But they're intuitive to casual users, and the so the interface leads casual users down garden paths that an outside bookkeeper will eventually have to fix before tax (or worse, audit) time. I've earned plenty of money fixing the problems that QBO leads casual users into, but I wish it didn't encourage them into those problems in the first place.
I also find the GUI distracting and obscuring in its own right. So much screen real estate is spent, even in the Ultra Compact display mode, on graphics that are supposed to be user friendly that I can never see as much actual financial information as I would like on one screen.
Also, the bulk-editing functions in the accountant version of QBO are hobbled compared to those in QB Desktop.
If you really must use QBO, do not use it without guidance if you do not have a solid working knowledge of accrual accounting; hire someone who does to do your bookkeeping instead.
If you have bookkeeping needs that are at all complex, I strongly encourage you to consider hosting QB Desktop on an application server instead. If you aren't sure how complex your needs are, consult an experienced bookkeeper before you choose your platform.