Essential mods for a first Fallout New Vegas playthrough?

If you want a list to follow rather than piecing it together, Viva New Vegas is the guide most people use. It's kept up to date and it's mostly fixes and stability, so it doesn't change the game on a first run.

Get the engine fixes before anything else. They matter more than any content mod. The usual base is the 4GB patch (lets the game use more memory, stops a lot of crashes), NVSE, JIP LN NVSE and YUP for bug fixes. Add NVTF if you get stutter. Install through Mod Organizer 2 and you can undo anything without breaking the game. For a first run I'd stop there, maybe add a UI mod if the text is too small. The vanilla game is the point the first time. If you want a step-by-step, most people follow the Viva New Vegas guide.