Cloud computing has a key requirement for resource configuration in a real-time manner. In such virtualized environments, both virtual machines (VMs) and hosted applications need to be configured on-the-fly to adapt to system dynamics. The interplay between the layers of VMs and applications further complicates the problem of cloud configuration. Independent tuning of each aspect may not lead to optimal system wide performance. In this paper, we propose a framework, namely CoTuner, for coordinated configuration of VMs and resident applications. At the heart of the framework is a model-free hybrid reinforcement learning (RL) approach, which combines the advantages of Simplex method and RL method and is further enhanced by the use of system knowledge guided exploration policies. Experimental results on Xen-based virtualized environments with TPC-W and TPC-C benchmarks demonstrate that CoTuner is able to drive a virtual server cluster into an optimal or near-optimal configuration state on the fly, in response to the change of workload. It improves the systems throughput by more than 30 percent over independent tuning strategies. In comparison with the coordinated tuning strategies based on basic RL or Simplex algorithm, the hybrid RL algorithm gains 25 to 40 percent throughput improvement.