Content-aware systems and methods for improving de-duplication, or single instancing, in storage operations. In certain examples, backup agents on client devices parse application-specific data to identify data objects that are candidates for de-duplication. The backup agents can then insert markers or other indictors in the data that identify the location(s) of the particular data objects. Such markers can, in turn, assist a de-duplication manager to perform object-based de-duplication and increase the likelihood that like blocks within the data are identified and single instanced. In other examples, the agents can further determine if a data object of one file type can or should be single-instanced with a data object of a different file type. Such processing of data on the client side can provide for more efficient storage and back-end processing.