I loved both games. Me and my friend have had this debate between oblivion and FO3 going for a while now basically he says its oblivion with guns, I felt it was much more. IMO FO3 attributes where far more balanced. For example, in oblivion you could make a knight style character, but ultimately nothing stopped you turning into a mage unless your a strict roleplayer. With FO3, if you spec in one area such as small guns, you can still use energy weapons but you do notice the difference, even in lower difficulties. FO3 also has the option of being played like a FPS without using VATS which adds a nice challange. Another challange is trying to play it without using weapons, ie sneaking, hacking, lock picking and charming to get everything. Certainly not easy. I was disappointed in oblivion after morrowind but feel that that FO3 has fixed some of the changes I felt didn't work in oblivion.
Mass effect on the other hand the story lasted what felt like forever. While I only replayed it twice I loved the combat and controlling you squad. each class offers something different but not enough to make me want to play though all 6 times. The karma in mass effect didn't work that well either compared to FO3. In dialogue you get 3 options, good, neutral or evil response. The evil responses just didn't fit in at all, just the tone of voice and how the conversation went it just felt like it wasn't meant to be there.
I would go for FO3. Again I had huge problems until I got it patched and GPU drivers sorted (It still doesn't like me using alt+tab). Mass effect Ive had no problems with so far touch wood.