EnergyPlus vs E+ GUI: Which to Choose

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I'd like to create a reference documenting the benefits and drawbacks of using EnergyPlus natively or GUIs (OpenStudio, Design Builder, and Honeybee) for different types of analysis or projects. Besides the fact that the GUIs do not have access to all E+ objects, can anyone help me understand:

1. Which is recommended for large buildings (>50-100 zones), as far as speed goes? I've noticed the OS GUI can slow down significantly with large buildings.
2. Which is recommended for LEED or compliance models?
3. I've only used Honeybee for single-zone box models/parametric studies. Does anyone use it for more than this?
4. What other tools do you use to plugin to these - jEPlus, etc?
5. Other considerations when choosing E+ vs an E+ GUI for a project?