The extraction of geothermal energy in the form of hot water from sedimentary rock formations could expand the current geothermal energy resources toward new regions. From previous work, we observed that sedimentary geothermal reservoirs with relatively low permeability would require the application of enhancement techniques (e.g., well hydraulic stimulation) to achieve commercial production/injection rates. In this paper we extend our previous work to develop a methodology to determine the optimum well configuration that maximizes the hydraulic performance of the geothermal system. The geothermal systems considered consist of one vertical well doublet system with hydraulic fractures, and three horizontal well configurations with open-hole completion, longitudinal fractures and transverse fractures, respectively. A commercial thermal reservoir simulation is used to evaluate the geothermal reservoir performance using as design parameters the well spacing and the length of the horizontal wells. The results obtained from the numerical simulations are used to build a response surface model based on the multiple linear regression method. The optimum configuration of the sedimentary geothermal systems is obtained from the analysis of the response surface model. The proposed methodology is applied to a case study based on a reservoir model of the Lyons sandstone formation, located in the Wattenberg field, Denver-Julesburg basin, Colorado.