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If you have a good flat clean parallel surface on the joints, the glue joint (titebond or equal) will be as strong or stronger than the wood itself as long as you don't starve the joint, but do clamp it hard enough to squeeze out the excess.
When you use a common term like "2x4", I tend to think you are using a stock lumber like pine. If so, you will need to joint the factory edges to get a strong glue joint. If the surface of the boards are flat (run thru a planer), you can also get by with a good quality fine-toothed blade in the table saw (one that gives a "glue line" face on the cut) . If you are planning on using a plane to finish the top, you want all the boards to have the grain running the same direction to prevent tear-out.
Making a 5 x 5 table top is no easy task. Good luck and take pics for us when you get it done
My advise is that biskets are easy to install and they increase the glue area on the joint. As stated above the glues currently available will be stronger than the original wood if the joint is prepared and glued correctly. The biskets will add strength, make the joint easlier to align during the clamping, and maybe give you piece of mind that the joint is secure.