Getting peoples' or animals' eyes in focus makes a big difference. We're drawn to look at them and if they're in focus we feel the image is in focus.
For macro: Absolutely use a tripod. And you preferably focus by turning off autofocus and doing it manually; or, better, set lens focus first (that sets the magnification), then focus the image by moving the camera. A small macro focusing rail is great for this and is not expensive.