There's the Neverwinter Night's series and BG series as everyone else mentioned, though you'll still have to be familiar (or get familiar) with D&D 2nd and 3d edition rules (NWN 1 = 2nd edition, NWN 2 = 3rd). Though, they're a bit more friendly then Baldurs Gate when it comes to those unfamiliar with the rulesets. Of course, they're not 1:1 to the PnP rules like Temple of Elemental Evil.
As YEPP mentioned, there's the Vampire series. Redemption is more of a party-based isometric clicker in 3D. It's a bit more traditional, and takes place in both medival times and modern times. Bloodlines is the newer of the two and has a Deus Ex feel to it: it's a FPS/RPG hybrid with open ended quests set in modern times. They did a decent job and translating the pen and paper rules, though not great. And the AI in Redemption is something you will cry over :/
Arx Fatalis was a pretty interesting game. Though gameplay wasn't anything new, the world it was set in was unique. Divine Divinity and the Gothic series are some gems in the rough, though can easily be overwhelming. DD is a bit linear so it's not as overwhelming as Gothic, but a fun romp if you like very challenging games. Just make sure if you do go Gothic 1/2/3, you get the fan patches as that really tightens up the loose ends and bugs.
Gothic 4/Arcania is a game that'll push your video card for sure, though that's half good graphics, half bad port job. However, it's Gothic only in name. Honestly it's more on the Adventure side of the genre rather than RPG (ala Zelda vice Fallout). Still, it's fun if you go into the game and don't expect a full JRPG/CRPG experience and more of an adventure type game.
If you want a JRPG on the computer, get Septerra Core. It's a hella fun game (bit grindy at times, though) with some nice sprite based graphics and unique party members. It's definately old school, but is about as close to a traditional JRPG as you can get on the PC.
There's the Fallout series, as prior mentioned, that's really good. Fallout Tactics isn't even half bad if you really, really like the combat from Fallout 1/2. Planescape is solid, as is Arcanum (midget pyromaniac FTW!). Icewind Dale is good if you enjoy the combat side more than the story side of the Baldur's Gate games.
If you don't really dig star wars, you can get Jade Empire. It's Star Wars KOTOR with a Crouching Tiger, Hidden Dragon twist and a different combat scheme -- real time interactive rather than action queues or turn based.
Two Worlds is good if you prefer more of a hack'n'slash approach to your RPGs. The storyline is thin as cellophane, and I can't decide if the voice acting is ye-old-world good or laughable. But, it does have a huge open eneded world, you can ignore the main quest if you want, and there's TONS of different types of arms, armor, and magic to get.
Finally -- I think -- there's the first person RPGs such as the entire Elder Scrolls series and Fallout 3. All good in their own rights, though the Elder Scrolls has been more and more simplified with each version since 2 (I miss being able to jump in a pool and heal 🙁 ).
