An important thing to note is that your score during the game includes your skull multipliers. So the only thing you will get at the end of the game in addition is the time bonus.
So if you have lost a great deal of your time bonus, then don't continue to play the level thinking there is more bonuses at the end, because there is not.
It is your style of play that determines the skulls you activate. My best advice is to play on Normal. The reasoning behind this is that where Legendary will net you points, you have a better chance of hitting the time bonus on Normal, and you can have more skulls on at once and it still will not be a big deal. Thus more bonus points.
Start with three or four skulls on, and see how you do? If it is too hard, then start over and remove a skull.
One the other hand, if you can net the required amount of points, then the time means nothing. On Tsavo Highway for instance, I hit the 15,000 points in game. So I just jumped in a ghost and skiddaddled to the end (running through the rest of the action), and got the achievement.
And don't be afraid to die a few times, on Normal you don't lose that many points. Of course on Normal you shouldn't die all that much either. Time is the biggest bonus, try for that before you waste time lining up every headshot and multi-kill.