Physical-layer cooperation has been demonstrated to vastly improve wireless link reliability and end-to-end throughput by exploiting spatial diversity. Nevertheless, its performance in operational networking environments is uncertain. Cooperative link gains can be potentially diminished by factors such as i) increased transmission footprint due to the activity of the cooperative relay, ii) non-ideal node location due to the structure of a planned network, or iii) the inability of cooperation protocols to recognize the channel's global state, hence leading to increased congestion. In this work, we identify and evaluate these key factors affecting the performance of cooperative techniques in small- and large-scale topologies. Our evaluation reveals that throughput gains from cooperation achieved in atomic, isolated topologies, decrease significantly when implemented at network-scale scenarios. Furthermore, our study provides a deeper understanding of the regimes in which cooperation performs poorly, and can help in the design of effective protocol solutions for such cases.