We propose a methodology for optimizing the reliability, power, area, and performance of Field Programmable Gate Array (FPGA)-based systems at run time based on dynamic reconfiguration. A partial reconfiguration manager is designed to switch between different versions of the design according to real operating conditions. Reliability, Power, area, and performance are factors used for selecting the design version to be configured. Power and Reliability conditions are assessed through monitoring the system power state and the environment radiations with a radiation sensor, respectively. The experimental results show 40% reduction in power consumption while keeping an average reliability of 99.5%