We use a generalized pore network model in combination with image-based experiments to understand the parameters that control upscaled flow properties. The study is focued on water-flooding through a reservoir sandstone under water-wet and mixed-wet conditions. A set of sensitivity studies is presented to quantify the role of wettability, pore geometry, initial and boundary conditions as well as a selection of model parameters used in the computation of fluid volumes, curvatures and flow and electrical conductivities. We quantify the uncertainty in the model predictions, which match the measured relative permeability and capillary pressure within the uncertainty of the experiments. Our results show that contact angle, initial saturation, image quality and image processing algorithm are amongst the parameters which introduce the largest variance in the predictions of upscaled flow properties for both mixed-wet and water-wet conditions.