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: 
Here's another point: many modern converters are protected against shorts or overloads in the output circuit. Such protection is a must for lab PSUs and a nice feature for all PSUs with connectors, since the ability to connect different loads increases the risk of shorts and overloads.

Having a big cap on the output reduces the effectiveness of such protection, since more energy is available to do the damage before the protection cuts the power off.
Larger capacitors also have more parasitics (eg equiv. series resistance and inductance.) This is what "slows them down" so to speak.