I don't really think it makes a difference.
For me, I use it when the magnitude of the project is enough to warrant a subdomain.
So, for example I am still working on that CSE idea.
CSE directories « Blind Ape SEO
Search engines for every idea are going to take up multiple directories and such, so I am keeping the focus areas targeted by using subdomains.
To make this more understandable:
I have a portal with custom search engines. One area might be trains.
It'll have sub-areas like steam trains, electrical trains, model trains, history of trains, european train history, etc...
All those already occupy an extensive dir-tree.
Now that I want X more areas to branch out into, subdomains make sense.
Thus I'll have
trains.myspamsearchengine.net
goldfish.myspamsearchengine.net
wickedfire.myspamsearchengine.net
neurology.myspamsearchengine.net
breastimplanst.myspamsearchengine.net
This might actually give me an advantage, because some search engines consider both
1. the position of the search term in the URL ("trains")
2. the length of the URL "trains.spamsearchengine.net" vs. "www.spamsearchengine.net/topics/trains"
Overall, I don't think it makes a lot of difference other than organization.
::emp::