See screenshot below for an example of how to create an F&F backup of an entire drive with some folders excluded:
The D drive is selected in the browse interface just like any other folder, and the folder exclusion field is populated just like the examples provided in the description below that field.
If you want to make a Full backup and do Differential backups later, then after you configure your backup, make sure to keep the checkbox to save your job selections as an XML file enabled. Then when you want to run a Differential, go to the Backup Definition Files tab, right-click the job, and select Run Now > Differential. You can also schedule backups of various types instead of or in addition to manual executions. When you ask Reflect to create a Diff, it will automatically be created as a child of the most recent matching Full at the destination. When dealing with F&F backups, what constitutes a "matching backup" can be configured in the settings of the job under Advanced Options > Backup Set Matching. In general you'll want to keep the default though.
I'm not sure what confused you, but if the cues in the interface don't help you get where you're trying to go, you might also consider looking at Reflect's online user guide, which you can access under the Help menu in Reflect. Macrium's documentation is better than most.