I have a buddy with a late 90s Mercury efi 2000. Recently it started becoming hard to start when cold, it seems to idle rougher than normal, and it’s really sluggish on the first initial takeoff of the day. Sometimes he can rev it to almost “clear it out” and then it will seemingly be fine and plane out like normal. After the first initial takeoff it acts totally normal the rest of the day. Busts right off on the first key turn and gets up on plane just like usual. I’m thinking it’s a fuel or fuel delivery issue. Anyone else have any suggestions?

Does he pump the primer ball hard to start the day?  Merc motors need a hard primer ball for cold start. Pump as hard as you can and then give it one more. 
 

I assume he’s changed the plugs recently. 

Most of the time, once you get past the basic stuff like making sure it has fresh gas, clean filter/water separator, spark plugs etc, EFI motors require hooking the computer and diagnostic software to them to troubleshoot.  If he doesn't have that, it might be getting time to bend over and grease up, because it's coming.