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: 
On the face of bigger is better for reasons that are well documented elsewhere.If the cap gets really big there will be problems with inrush current .On a small power supply the transformer should keep this down to a reasonable value .When rectifying mains into a cap filter the peak currents in the diodes can be several times the average DC output current .This is well documented elsewhere.This peakiness of diode current causes poor power factor and bad line current THD .If your source impedence is low the bigger cap will make this worse .Generally you can use the bigger cap on a small transformer based system without having to add any other parts.Larger systems can be made to work well by employing a line reactor on the AC or a small choke on the DC .If you are putting a very large smoothing cap on the output of a buck convertor there is a risk of instability which may need a small inductor to mitigate by divorcing the big cap.
Larger capacitors also have more parasitics (eg equiv. series resistance and inductance.) This is what "slows them down" so to speak.