Large-scale cyber-physical systems, such as those for subway transportation or air traffic control, are becoming increasingly complex and often need to operate without human intervention. At the same time, these systems are subject to high requirements on the timing behavior and fault-tolerance. Consequently, the detection and mitigation of both hard and soft errors is of high importance in the already complex systems design process. The main challenges towards fault-aware real-time systems is the overall system design, in which the sheer size of the state-space and the systemtextquoterights complexity exceeds the capacity of todaytextquoterights development tools. In this paper, we present a new holistic methodology called FAA+RTS, for designing fault-aware adaptive real-time systems. We cover the entire path from system specification using a coordination language, via design-space exploration and task scheduling to the adaptive fault-aware runtime environment. Mitigating both hard and soft errors addresses competing requirements. Improving soft error tolerance (through redundant execution) may accelerate the aging process of silicon, thus expediting hard error failures. FAA+RTS is a novel solution as it integrates previously-isolated methods for dealing with multiple constraints into a single framework, presenting a single overview of all possible trade-offs to the application designer. This integration ensures that all aspects of system design, from specification to execution, are cohesively addressed, resulting in a robust and reliable system. We exemplify FAA+RTS using industrial-sized autonomous subway transportation system as a use-case.