Quick analysis of the two SD-Denver matchups during the regular season, for whatever that's worth.
Game 1: Den 28, SD 20 (in SD)
Denver won largely due to a great game by Manning: 25-36 (69.4%), 330 yds, 4 td, 0 int. SD won the T.O.P. battle (38:03 to 21:57) and the turnover battle (1-0), but simply could not stop Manning. The game was 28-6 Denver before SD scored two TDs in the 2nd half to narrow the margin. SD cut the lead to 28-20 with 10:42 left in the game, and at that point, things were pretty interesting. Plenty of time for SD to come back, since they had scored 14 straight points and had momentum. Denver was actually forced to punt at that point, giving SD the ball back with 6:43 to go, down a score (and 2-point conversion). They actually got a first down at their own 45, moving the ball well, but then this three-play sequence did them in: Rivers fumbled (and recovered) at their 41, loss of 4. Rivers sacked by Miler, loss of 2. Then Rivers threw incomplete deep to Royal. SD had to punt. Denver then ran out the clock using a few key Manning passes to keep the chains moving.
Game 2: SD 27, Den 20 (in Den)
SD won largely due to a huge disparity in rushing, as they out gained Denver 177-18 on the ground. Matthews was terrific, and Denver couldn't do anything in that department. Manning was pretty solid again (27-41, 289, 2 td, 1 int), and Rivers didn't have to do much (12-20, 166, 2 td, 0 int). SD once again won the T.O.P. battle (38:49 to 21:11), and also won the turnover battle (1-0). This time they managed to make the plays when they needed to make them. They got up 24-10 and held on for the win.
If the first two games gave us anything to go by, SD will run the ball effectively against Denver, and will dominate time of possession. I don't see that changing, unless Matthews can't go. And even then, I think they can probably do a lot of damage on the ground. That'll be their game plan, and I think they'll do a good job executing it. They've held Denver to 48 points (24.0 per game) and 692 yards (346.0 per game), well below their season averages of 37.9 points and 457.3 yards.
I think SD can keep this a close game, and from there, it's really a matter of who makes the key play. Denver is rightfully the favorite, but SD very much has a real shot at this.