Question: I work with low-power DC voltage regulators. I am already aware of the formula to calculate the size of smoothing capacitor(s). This can be an iterative process of testing one size with a scope and then using a larger size or adding more until the scope shows acceptable (very low) levels of ripple and noise.

Besides the cost of the capacitors, is there any tradeoff to rounding up (a lot) and just using a very large capacitor(s) rather than trying to calibrate the sizing to "just enough" but not more than that?

Answer: 
As far as caps go, there are two competing requirements:long-term (ripple) and instantaneous (spike). A big electrolytic can give you the former but not the latter. Generally you parallel your large electrolytic with a smaller 0.1uF capable of supplying that instantaneous spike whilst the electrolytic lumbers into action. Or the 0.1uF may be for local decoupling to stabilise that regulator. If the specified capacitor is actually 0.1uF or smaller, then the intention of the capacitor is to supply small amounts of charge very fast. Do not replace this with a bigger electrolytic - that's definitely a case where larger is worse not better.

Going past that, you'll have to tell us what kind of regulators you're dealing with. If it's just a basic linear regulator then it doesn't really matter. If you have a switching regulator though, the capacitor will affect the resonant frequency of the switcher, so be very careful there.
Note: my interpretation of the OPs post is we are talking about capacitors on the output of voltage regulators, some other posts seem to assume the asker is talking about capacitors on rectifiers.

The main downside of a bigger capacitor is that the switch on rise time and switch off fall time will be greater. That means more stress on the regulator during startup and in extreme cases may even cause an overcurrent shutdown of the regulator. It can also cause problems for loads which don't handle undervoltage very well.

Having said that I don't think there is any point trying to micromanage the size of such capacitors. In most cases allowing a generous margin (a factor of 2 or more) over what you think you need is unlikely to be a problem.