The ecu has what are called 'adaptive strategies' that allow it to alter how it thinks. Over time it will make adjustments for things -- like sensors that aren't as effective as they used to be, and even driving style. There is a limit to how far it can alter things as it 'learns' about changes that are occurring. So it has some ability to adjust even with the O2 sensors gone.
No doubt -- the further you change things beyond what the design engineers of the ecu had in mind for it's operational parameters, the more likely you're gonna need to alter the ecu (chip, pms, tweecer, etc.) - with or without O2 sensors.
There are a number of tuners out there who prefer to do their heavy-mod tuning (lots of boost for example) with no O2 sensors so the computer stays in open loop.