1) Decide where the instructions come. If the first 5 fields are simple and don't need any help I would omit instructions on top. My inspiration was to be as contextual as I can.
2) Visually, I like instructions identified on the right corner with either a prominent font, OR a color OR maybe a background. (Use only one or two methods but sparingly without taking attention from the form). Surely follow the visual design of the entire website or software if it is decided.
On this page, the form starts on left and instructions on the right along side. Users get the flow instantly (my guess)
3) Content wise, I feel instructions should be clear, friendly and should really help. Title for the instructions if any should be in easy to read language. Less technical if possible. Lastly, I try hard to be as comprehensive as I can and that you rightly pointed out.