I had a frame shop for many years and generally you only need glue to hold the joints together. There were some issues when we were using Elmers white glue, but then Framica came out with Corner Weld glue and those issues disappeared. We used underpinners for the corners, but they were in place of clamps to allow us faster production. They added little in way of strength.
Any clamp that holds the corners tight and square is going to do fine. Cross nailing the corners with either a brad nailer or by pre-drilling and driving conventional brads.
This is the vise I used for corner nailing when required: https://s3.amazonaws.com/images.tool...S-D3227__1.jpg
Four Bessey or Pony corner clamps will work also. They cost about $10.00 each. They seem quite accurate.
When Corner Weld first came out I did a test on the glue vs. Elmers. There was no comparison. The Corner Weld was vastly stronger.
Just recently I did a test of Corner Weld vs. Woodworkers III glue. The strength results on miters was almost exactly the same (I used weights and they both failed between 35 lbs and 40 pounds on a 3/4" x 3" stock with an arm of 14").
The main advantage of Corner Weld is that is sets up so fast. If you apply glue to both surfaces and press and rub togther in about 30 seconds they are tacked together. In five minutes you can handle the joint. In two hours you can assemble the frame.
The WWIII takes ten minutes to setup and I would not handle the parts for at least 4 hours.
On the otherhand Corner Weld would be a disaster when doing a complicated glue up. It would set before you were done positioning things.
Picture frames are not subject to much stress. The biggest enemy of picture frames is wide molding (3" +) and seasonal wood movement. After several seasons you can see joints popping apart.
Always hang the frame from the verticle frame members and about 1/3 of the way from the top. That minimizes stress on the joints.