Focusing and tripods don't matter. It's motion blur you're worried about.
Partly it's the faster apertures, but it's mostly the focal length. The rule of thumb for eliminating camera shake blur from handheld photos is to shoot with a shutter speed of 1/
focal_length or faster (without stabilization). Obviously, this presupposes good handholding technique and relatively steady hands. There is a lower bound (for me, it's around 1/30s), and people do differ on their handholding ability.
With a 50mm lens, by this rough rule, you only need to be shooting at 1/50s or so. With dSLRs giving you iso settings up to 1600, this often isn't that hard to achieve, especially with a fast lens.
However, if you're shooting with a 300mm lens, then the restriction is 1/300s, and IS becomes more useful, which is why Canon's 70-300 and 300 f/4L are both IS lenses.
Remember, too, that IS only acts like a tripod or monopod: it's only good at steadying the camera and does nothing for reducing subject motion blur--only a faster shutter speed can achieve that, and that will depend on your iso setting and how wide you can open the aperture.