As aggressive integration paves the way for performance enhancement of many-core chips and technology nodes go below deca-nanometer dimensions, system-wide failure rates are becoming noticeable. Inevitably, system designers need to properly account for such failures. Checkpoint/Restart (C/R) can be deployed to prolong dependable operation of such systems. However, it introduces additional overheads that lead to performance variability. We present a versatile dependability manager (DepMan) that orchestrates a many-core application-level C/R scheme, while being able to follow time-varying error rates. DepMan also contains a dedicated module that ensures on-the-fly performance dependability for the executing application. We evaluate the performance of our scheme using an error injection module both on the experimental Intel Single-Chip Cloud Computer (SCC) and on a commercial Intel i7 general purpose computer. Runtime checkpoint interval optimization adapts to a variety of failure rates without extra performance or energy costs. The inevitable timing overhead of C/R is reclaimed systematically with Dynamic Voltage and Frequency Scaling (DVFS), so that dependable application performance is ensured.