During the Main Story you will be asked to make a number of decisions, most of which will significantly affect gameplay later on in the game. WARNING: There are major spoilers in this guide; this list has written in chronological order, so be sure to only read down as far as you have been in the game.
Mission Encountered: Ivan the Not So Terrible
Options: Either Spare or Execute Ivan.
Spare Ivan: Mission ends; Ivan appears as a Random Character after the "Actions Speak Louder Than Words" mission.
Execute Ivan: Mission ends, Ivan does not appear as a Random Character later on in the game.
Mission Encountered: Ruff Rider
Options: Either Spare or Execute Cherise.
Spare Cherise: Cherise appears as a Random Character after the "The Holland Play" mission.
Execute Cherise: Cherise does not appear as a Random Character later on in the game.
Mission Encountered: Holland Nights
Options: Either Spare or Execute Clarence.
Spare Clarence: Clarence appears as a Random Character after the "Blood Brothers" mission.
Execute Clarence: Clarence does not appear as Random Character later on in the game.
Mission Encountered: The Holland Play
Options: Execute Playboy X, Execute Dwayne.
Execute Playboy X: Unlock Playboy X's loft apartment (complete with pool table, parking spaces and the outfit from GTAIII), unlock Dwayne's friendship.
Execute Dwayne: $25,000.
Mission Encountered: Blood Brothers
Options: Execute Derrick, Execute Francis.
Execute Derrick: Attend Derrick's funeral in "Undertaker," earn one-time ability to call Francis during the Main Story to remove a Wanted Level.
Execute Francis: Attend Francis' funeral in "Undertaker".
Mission Encountered: That Special Someone
Options: Either Spare or Execute Darko.
Consequence: There is no affect on gameplay, you simply hear a different dialogue as you take Roman to Brucie's place. The Execution scene is worth watching though, and besides, you've come this far, so why would you waste the opportunity?
Mission Encountered: Finale (just after That Special Someone)
Options: Take Jimmy's Deal, or seek Revenge.
Deal: The Finale mission strand will take place as follows: If the Price is Right => Mr. and Mrs. Bellic => A Revenger's Tragedy.
Revenge: The Finale mission strand will take place as follows: A Dish Served Cold => Mr. and Mrs. Bellic => Out of Commission.