as Sjizzle says, there are a few good Mega Mods out there, but I didn't really use them (my computer was not the best before I upgraded it)
If your not going to use a Mega then I highly recommend the following:
Mighty Fine Crew Mod- makes the crew actually "work" and has options to change how they look etc (beards for example)
Open Horizons II- great mod that extends the campaign and adds some new missions etc. (it does more than that, but it's late here

)
IRAI- Ship AI mod that makes the friendly and enemy ships behave more realistically.
I could name more, but those are some good ones to get started with. Basically just cruise the Downloads section, and see what takes your fancy. There are some very talented people making mods these days.
Happy Sailing, and Good Hunting!