Carrying out science at extreme scale is the next generational challenge facing the broad field of scientific research. Cloud computing offers to potential for an increasing number of researchers to have ready access to the large scale compute resources required to tackle new challenges in their field. Unfortunately barriers of complexity remain for researchers untrained in cloud programming. In this paper we examine how cloud based architectures can be used to solve large scale research experiments in a manner that is easily accessible for researchers with limited programming experience, using their existing computational tools. We examine the top challenges identified in our own large-scale science experiments running on the Windows Azure platform and then describe a Cloud-based parameter sweep prototype (dubbed Cirrus) which provides a framework of solutions for each challenge.