Trace Flag 4199 - Enable globally?
Personally, whenever I build a new server for a new project I always enable TF4199 globally. The same applies when I upgrade existing instances to newer versions. 

The TF enables new fixes that would affect the behaviour of the application, but for new projects the risk of regression is not an issue. For instances upgraded from previous versions, the differences between old and new version are a concern on their own and having to deal with plan regression is expected anyway, so I prefer fighting with it with TF4199 enabled.

AS far as existing databases is concerned, there is only one way to know: test it. You can capture a workload on the existing setup and replay it after enabling the flag. RML Utilities can help you automate the process, as described in this answer.

Obviously, the flag affects the whole instance, so you'll have to test all the databases sitting there.