Its always wise to buffer any signal going to/from the 'outside world'. Also for conformance with the CE directives you need to protect to inputs/outputs from accepting or radiating EMI and suseptability to ESD transients.

For low frequency inputs, re-arranging your R & C so that you get a low pass filter helps to protect against ESD as well as giving some overvoltage protection. Be aware of the effect of this R & C as it affects risetime! You can add MOVs and/or transzorbs for superior protection. It always pays to think what voltages might appear on an input in normal (ab)use. One instance is RS485 - on my equipment there is 24VDC also present so one might think a customer might wire 24VDC to the RS485 connections. The poor old transzorb will die and propably go up in smoke - not good. So I add a polyswitch in series so that it limits the current to the transzorb. If someone wires 220VAC to it there will be smoke - but they would have to be real stupid!
Find yourself a old fuel injection computer from a car and observe what techniques they use - in most cases they have a R & C on every input.

Remember that MOVs have a fair amount of capacitance that varies from manufactuter to manufacturer whereas transzorbs have very little capacitance - therefore transzorbs are generally better for higher speed signals.

Say you have a high current switched output, its wise to put current limiting on this so that a short circuit won't cause smoke.

All these extras add complexity to the design but add a whole lot of robustness.

There's plenty written about these issues on the web.