Warning:
If you are new to Mod Organizer 2, it can be daunting. I recommend reading the Nexus description page for some information, and also to click on the tutorial during installation.

Completing The Setup Wizard

• Open Mod Organizer 2 
• Download the main file, and run the executable
• select I accept the agreement and click Next >
• Click browse and navigate to X:\Skyrim Enhanced
• With X:\Skyrim Enhanced highlighted, click Make New Folder
• Click OK
• You should end up with X:\Skyrim Enhanced\MO2
• Click Next >
• Click Next >
• Click Next >
• Click Next >
• Click Install
• Make sure Launch Mod Organizer is checked, and click Finish
  

Creating A New Instance

• Make sure Never show this page again is unchecked
• Click Next >
• Select Create a portable instance
• Select Skyrim Special Edition
• Make sure your location is set to X:\Skyrim Enhanced\MO2
• Make sure Show advanced options is unchecked
• Click Next >
• Click Finish
  

Setting Up Mod Organizer 2

The Vanilla profile:

• Click Yes to associate MO2 with Nexus links
• Click the ID Card icon on the Main Toolbar
• Click Create on the right side of the window
• Check Default Game INI Settings, and name the profile Vanilla Skyrim
• Click OK
• Close the menu and use the profile drop-down menu to select the newly created profile
  

The Skyrim Enhanced profile:

• In the Left pane of MO2, drag and drop DLC: Dawnguard to the top of the mod list.
• Select the ID Card icon once again
• Highlight Vanilla Skyrim and click Copy
• Name the profile Skyrim Enhanced and click OK
• With the Skyrim Enhanced profile highlighted, check Use profile-specific Save Games
• Highlight the Default profile and click Remove
• Close the Profiles menu and make sure Skyrim Enhanced is selected in the Profile drop-down menu
  

A Few "Quality of Life" Tips

Changing the theme:

• Click the Settings icon (wrench and screw-driver)
• Under the Theme tab select Paper Dark
• Close the settings menu
• Right-click in the empty area at the top of the MO2 UI
• Uncheck Menu, Status bar, and Log
• Check Large Icons and Icons and Text
• Right-click in the area under Overwrite and click Create separator
• Name it Official Bethesda Master Files
• Move the newly created separator above DLC: Dawnguard in the left pane of MO2
  

Adding the MO2 icon to your taskbar:

• Right-click on the MO2 icon on your Windows taskbar and click Pin to taskbar