*Mass Effect 1 Spoilers Ahead*.
When I first started playing games that had moral choices, I would invariably go for the evil path first and foremost, because it was easiest, and it was damn fun being an evil bastard. The one thing I've always had problems with was the Love Interest. In KoTOR, I hated myself for abandoning Carth to go with Bastilla.
The first time I played a "good" character before an "evil" one was Mass Effect 1. I have no problem with the day-to-day Renegade choices (threaten a police officer, shoot a pirate rather than arrest him, that sort of thing), but when it comes to the big choices, and interactions with my crew, I have no stomach for it. In fact, my one Renegade character ended up "switching sides" during the Feros mission, to avoid killing the colonists and later, to save the Council. Killing the Rachni, who once started a galactic war, was one thing. Shooting Fist was one thing. Being borderline xenophobic was one thing. But killing 24 innocent men and women when there was an easy alternative is just plain unconscionable. Likewise with the Council. They may not have always been humanity's best friend, but they were the best hope for stability and peace. To jeopardize that for the sake of a few thousand humans is nigh unthinkable.
The much lesser guilt comes from being a dick to your crew. No matter what you say to them or what reprehensible things you do, they still follow you, either out of necessity or respect. When you trample all over that respect, it makes you feel like an asshole. These are good people you're insulting here, not some smug terrorist. They react to your vitriol, and it fills you with shame.
There is of course the Sadistic Choice on Virmire: Ashley or Kaidan. If you save your Love Interest, it makes you understand exactly why there are regs against fraternization. If you choose the non-Love Interest out of pragmatism, you wonder what kind of desensitized jackass you are, to leave your lover to die because they weren't part of your favorite squad. If you chose Liara, the choice becomes even more arbitrary and cold-hearted. You likely don't have a personal stake in either of their lives, and therefore choose one over the other for no particular reason at all.