This really depends on what you want and how much experience you've had with the game.
Many mods add new quests, but some of those are supposedly for experienced BG players only.
The fix/tweak mods smooth out the gameplay experience, but some components could be considered cheats. If you are a purist, read the readme files carefully.
Do you want more party interaction? Romances? Are you male or female?
I personally wouldn't play the game without these mods:
BG2 Fixpack:
http://www.gibberlings3.net/bg2fixpack/
NPC mods
BG2 Tweak Pack:
http://www.gibberlings3.net/bg2tweaks/
Widescreen mod:
http://www.gibberlings3.net/widescreen/
The above should be the rec. installation order. Do read the readme files before installing.
There are lots of NPC mods. Many (most?) include romances, but these are optional. Some NPC mods are rubbish, but there are surprisingly many good ones. I'd say the best ones are at least as good or better than the original Bioware characters in terms of writing. Some of the most popular NPC mods seem to be these:
Xan:
http://www.pocketplane.net/mambo/index.php?option=com_content&task=blogcategory&id=164&Itemid=113 Angelo:
http://www.gibberlings3.net/angelo/
Kivan:
http://www.gibberlings3.net/kivan/
Gavin:
http://www.gibberlings3.net/gavin_bg2/
Edwin (adds a romance component to an existing NPC):
http://www.spellholdstudios.net/ie/edwin Sarah (includes a lesbian romance):
http://www.gibberlings3.net/sarah/
Amber:
http://www.gibberlings3.net/amber/
de'Arnise Romance (adds a romance to an existing NPC):
http://www.pocketplane.net/mambo/index.php?option=com_content&task=blogcategory&id=119&Itemid=118 Warning: do not install the romance cheat components of the BG2 Tweak Pack if you want to install NPC mods. Unless you install the Crossmod Banter Pack, you can run multiple romances by default.
It takes a bit of work to mod the game, but it's worth it. They really do add to the experience.