Hub-and-spoke networking is a key feature of current aviation markets in which hubs, as connecting points, function to consolidate and redistribute flows. This indicates that observation of traffic on a segment does not necessarily convey information about the origin to destination routing of passenger journeys because of the unavoidable detours in the system. This paper examines the heterogeneity of the flow composition in domestic and international US markets, which in turn allows us to observe the variation of operations across major hubs. A modified Route Flow Estimator for origin-destination synthesis (or origin-destination matrix estimation) is designed to decompose the segment traffic into itinerary-based passenger trips. Several public and commercial databases, which are easily accessible, are exploited (and reconciled) for the model in order to (i) generate possible trip itineraries using those segment markets, and (ii) link data-driven operational conditions with the underlying segment flows. The results are validated with US domestic trip observations and empirical knowledge related to the air transportation system. Then, the variability of the hub operations is examined based on sensitivity tests using the model parameters. From the resolution of itinerary-based estimates, we observe that major airports' hub operations are spatially uneven, particularly with respect to domestic and international connecting passengers.