Full-system simulators are invaluable tools for designing new architectures due to their ability to simulate full applications as well as capture operating system behavior, virtual machine or hypervisor behavior, and interference between concurrently-running applications. However, the systems under investigation and applications under test have become increasingly complicated leading to prohibitively long simulation times for a single experiment. This problem is compounded when many permutations of system design parameters and workloads are tested to investigate system sensitivities and full-system effects with confidence. In this paper, we propose a methodology to tractably explore the processor design space and to characterize applications in a full-system simulation environment. We combine SimPoint, Principal Component Analysis and Fractional Factorial experimental designs to substantially reduce the simulation effort needed to characterize and analyze workloads. We also present a non-invasive user-interface automation tool to allow us to study all types of workloads in a simulation environment. While our methodology is generally applicable to many simulators and workloads, we demonstrate the application of our proposed flow on smartphone applications running on the Android operating system within the gem5 simulation environment.