Ok, the problems with GB flash cart design:
1) The size restriction. You only have a limited board area and only one side of the board is usable for components. (GG for a comparison has like the double board size available to it, and can also use both sides without problem.)
2) To a lesser degree power consumption of whatever you put on the board.
3) GB is 5 V whereas you'd need to go 3.3 V if you want a reliable stock of flash and RAM chips in reliable sizes. That means you need level shifters for the buses, or possibly a 5 V tolerant FPGA/CPLD as a bridge to the other chips. (Hard to come by these days...)
4) Games that use saving expect battery SRAM, which means you need a battery which takes up valuable board space, or more expensive FRAM or MRAM.
So far, there have been two designs around using USB.
1) The GBflasher design, used by Jose Torres and Smartboy. This design originally used a serial port programmer, but later added a USB serial chip and then moved it onto the cartridge board. It was a 5V design right through and worked well across all platforms. (Because of the FTDI drivers.) However, it was slightly overpriced for what it was and ultimately Jose Torres got caught with his pants down using this design, specifically not to be used commercially. So that cartridge won't be sold again, probably. Smartboy just disappeared from the surface of the earth.
2) The oh so beloved and hated EMS. EMS carts are using a custom flash controller, also used for some of EMS's other products like their N64 memory cards iirc. It's using a (I think) 5 V low-power FPGA, that they may have had to finalize the chip fab for themselves. (I looked into that long ago and as far as I remember, the producer of the FPGA sold this model of FPGA as wafers/dies.)
If it wasn't for its problems (power consumption, stuck page problem, proprietary drivers) it would be a decent cart. It's got enough memory to hold a lot of stuff and actually has multi-ROM capabilities. What this means is that each of the pages can be filled up to the memory size (with some limitations regarding ROM image alignment.) However, this has gotten a bit of a bad rap because it's known not to work well with LSDj in different ways. (LSDj is badly aligned by default and its SRAM management is not compatible with that of available menu ROMs.)
So, the future?
1) abrasive's drag'n'derp which features standard USB mass storage compatibility = works on all platforms. However, it keeps the creator is a heaps busy. Current status: The hardware design is mostly done but the software needs some touching up. Expected ETA: Early 2012.
2) krikzz' Everdrive GB. I asked him about this many months ago now and he said he hadn't started working on it. He may have started working on it now, but I haven't seen any sneak peeks or announcements about it. I'm suspecting he wants to leave it for last because of the difficulties mentioned above.
