I would have thought that if your making a door frame out of 3" by 4" the 4" will have the rebate cut into it. A single mortice and tenon for up to c 3" should have a ration of 1 to 3, or for 3" thick wood, a tenon that is 1" thick. Above this dimension, the wood will be prone to twist if you use a single tenon. Indeed some would suggest that a single tenon at 3" offers too little resistance to twist and two should be used above 2.5".
Incidentally the recommended maximum length of a tenon to prevent weakening the timber too much is c 5~6 times 1/3 of the thickness of the wood to be tenoned. Any longer than this and two tenons in a line should be used linked By a haunch tenon.
I have just completed a 4" by 3 " door frame in oak. I used two tenons for every joint. You want to try and spread out the tenons to be close to the outside edges of the timber to reduce the amount of twist that can occur. This however needs to be considered with practicality. I always try to align one tenon with the edge of the rebate so, that the tenon starts at the rebate, this both makes it easier to cut, and also offers the maximum support to the rebate when the door is slammed closed. I usual use two 3/4" tenons in 4" wide wood. However, depending on the moulding your adding to the frame I adjust this to make life easy. So, they normally vary between 5/8 and 3/4.
Leave at least 2~3" at either end of the head and cill to produce good tight Mortices and tenon joints. Open Mortices are not as effective when trying to get good glue up. Don't bother wedging the tenons as when you cut off the ends of the head and cill the wedges will become ineffective and create a shear force on the glue which it's not designed and and can cause the joint to fail. The focus should be on making nicely fitting Mortice and tenons that done need wedges to make the tenons fit properly.