A large deck, full of superfluous cards, will generally lose. If you have too many cards, and no particular theme, then you will never draw what you need when you need it. That is why you should try to trim your decks to 60 cards.
The first step is to eliminate those cards that are only real useful based on contingencies. Now you should be down to a medium-large deck with only self-contained good cards. To further trim your deck, allocate your cards into 1 of 4 categories: Offense, Defense, Mana, and possibly an "Other".
Go through your offense category. Choose the strongest cards, and get rid of the weaker ones. Generally, you should have 4 of each card to improve the chances of you drawing one, but sometimes less is better (depending on the card).
Choose your defense. Choose defensive cards that fill in the gaps of your offense. For example, if your offense is all ground based, pick cards that get rid of flyers.
If you have an "Other", choose what seems appropriate and remove useless cards. It's up to you.
Add enough mana sources (lands, artifacts, and creatures) to support your deck.
A contribution to deck fat is trying to do too many things. A good, lean, deck can usually do 2 things fairly well; when you try to add a third capability, that's when the deck gets bulky.
About combos: if each card in the combo can serve a valuable purpose on its own, and the combo is even better, then use it. For example, Hunted Wumpus and Charisma. If a card is only useful in combination with another card, it's a good candidate for removal. The exception is when you base the entire deck around the combo, such as a deck revolving around Donate and Illusions of Grandeur. When you have a combo deck, the deck is made up of the combo cards and support cards, and your goal is to get the combo running as quickly as possible