In an earlier post you mentioned that you are using opto-couplers to drive some additional I/O. How is this I/O supplied (from a different source or from the same one) and if it's a different supply, does it have an equalized ground? If so, it's pretty useless.

Again, if your design is fully separated from any other device it's connected to(that's why you use the optocouplers in the first place), the supply is free from the mains (use a good transformer), there is only a small chance that your system will crash, even when hot-plugging. If you want to intercept that possibility as well, separate your board's serial I/O and to catch the last possibility of hang-ups, add a good uP supervisor. But first and for all you have to be 100% sure that your device is galvanically free from it's surrounding.