Hi Jaredirk
Definitely you will face issues and its not a best practise to have contrasting rules for the same group.
Ex. One rule to scan the windows\temp folder and another rule to not scan the windows\temp example in the default groups
on the default group, i didn't make exclude the windows\temp folder to be scanned then made a subgroup with exception to scan windows\temp folder.
Yes it is possible if you break the inheritance as Brian suggested. you can create multiple groups & subroups & assign different policyto each group. It will work.