In this paper, we propose a design paradigm for energy efficient and variation-aware operation of next-generation multicore heterogeneous platforms. The main idea behind the proposed approach lies on the observation that not all operations are equally important in shaping the output quality of various applications and of the overall system. Based on such an observation, we suggest that all levels of the software design stack, including the programming model, compiler, operating system (OS) and run-time system should identify the critical tasks and ensure correct operation of such tasks by assigning them to dynamically adjusted reliable cores/units. Specifically, based on error rates and operating conditions identified by a sense-and-adapt (SeA) unit, the OS selects and sets the right mode of operation of the overall system. The run-time system identifies the critical/less-critical tasks based on special directives and schedules them to the appropriate units that are dynamically adjusted for highly-accurate/approximate operation by tuning their voltage/frequency. Units that execute less significant operations can operate at voltages less than what is required for correct operation and consume less power, if required, since such tasks do not need to be always exact as opposed to the critical ones. Such scheme can lead to energy efficient and reliable operation, while reducing the design cost and overheads of conventional circuit/micro-architecture level techniques.