To be honest, some of the settings are a bit confusing. I am not your average user, but I am still having a hard time getting a grasp on all the settings. Sometimes I have no idea if I should be clicking allow/ok, or not, because there is not a whole lot of info. to make that judgment call.
I am just looking for the best way to make my PC safe & secure, but without having to constantly allowing or blocking items.
Any help would be greatly appreciated.

If your pc is clean and I mean clean then 99% of what Comodo is alerting you to is safe and can be allowed. Windows programs like svchost,explorer.exe and system should have a firewall policy of outgoing only. Comodo gives you 2 alerts. Some firewall and some D+. You need to read them. If you just tried to launch Yahoo Messenger and you get a D+ alert then click allow. If you just clicked update on your virus scan and get an alert then make that an updater/installer. Read the help file under Miscellaneous also. Set the firewall and D+ to safe mode also. Those settings are found when you open up Comodo and look on the main page. Once Comodo learns all your programs then you wont get any alerts ecept when you install something new. Be sure to read the sticky’s under important topics.

Thanks. I do have my settings on safe mode, what threw me off, was after I had run the last update, I got several pop-ups after I tried to run a few different programs: such as for allowing direct monitor access, and access memory.