I'm currently building a machine with almost those exact specs - 22"x42" cutting area. I also opted to go the tubular steel route and it is quite a bit more work. The frame, however, is very solid. You can take a look at my build thread for more details. For a first machine, a wood frame can work very well. There are many awesome examples of this on the zone. One of niceties of a wooden structure is that it is easier (for me at least) to modify.
If you have already decided to go the steel route, the next question becomes weather to bolt and epoxy or weld the frame together. Bolting and epoxying will allow for more accuracy, but if you are using homebrew skate bearings, I think the added accuracy may not be worth the effort. Welding can be a tricky proposition because of heat distortion; the cnc should be designed such that it allows for adjustments to compensate for a non-square frame. If you are using commercial linear bearings, bolting and epoxying might be warranted.
If you decide to bolt the frame together, you might be able to get away with slightly thinner-walled tubing such as 16gage 2"x2". Welding (especially stick) will require at least 11gage to prevent undue heat warpage. I went with .120 1.5" wall tubing for my structure, supported at intervals along the x any y axis. You can use a free program called "beam boy" (google it) to calculate the deflection on a beam with the given gantry weight and support structure. Plug in your particulars and this will get you in the right ball-park.
As a final thought, you can also use epoxy leveling to compenstate for slight amounts of distortion. I did this on my machine, but came to the conclusion that it was not warranted given the accuracy level of my other drive components. If you do decide to try this, make sure you have a WATERPROOF dam structure to trap the leveling epoxy - don't ask me how I know this ...