The most basic of mistakes can cause an agent to reject your manuscript before they make it past the first page (or a reader to stop reading). Some of them are mistakes even seasoned writers make. There is one easy, simple rule and it is this: By the end of the first page the reader must want to turn it. You have to pique their curiosity, their interest, and make them want to know more. If you annoy them with basic blunders though they won't want to keep going.
While most people love a bit of prose no one wants to drown in it. If you spend paragraphs describing something just be sure the tension is building, a question is forming in the reader's mind, or something interesting is happening. Also, do not pile information or back-story on the reader in the first few pages. Push yourself to see how many pages you can last without putting any back-story in at all. A prologue is different because it usually isn't an information dump, it's usually happening now. Try to avoid flashbacks if you can. They have their place in some manuscripts but certainly don't belong in every manuscript and are most powerful when used few and far between.
Avoid clique beginnings at all costs. Agents rarely make it past the first paragraph of a clique beginning. Some examples are; weather, answering the phone, and the morning routine. Strive for originality, not something you read in another book or saw on TV. Respect your reader's intelligence. You don't have to explain every little detail, either in description or conversation. If the typical person would know something you can leave it out. Happy writing!
Author of The Secret Of Spruce Knoll, Born Of Fire, Channeler's Choice, and coming in May of 2012, To Ride A Puca. A short story of Heather's is also available in the free In His Eyes eBook anthology.