I realise that the Mega has lots of pins, so it's going to need a long PCB but it would be much easier to use for prototyping than the conventional shield version.
The closest I've seen is the "Meduino Mega2560" but that has double row pins which make it impossible to use with a conventional breadboard.
Wouldn't be too hard to adapt this double sided board to single row connectors for breadboard use.
Would make for a pretty long board (even 4.4 inches just for the standard 88 pins, plus space for the chip), and another 0.6" if all 100 pins plus power/Gnd are brought out.
I think I'd go for a small dual-row board and make up some 1x10, 1x12, etc. cables to bring the signals to a protoboard.
Or 1x10,12, 16 or 2x whatever on one end and 1x8 on the other to breakout the 8-bit ports.
For example, this one, populate with male or female headers, and then use crimp housing and pre-crimped wires to make up what ever bundles were needed.
http://www.crossroadsfencing.com/BobuinoRev17/
Got a layout that will work nicely I think.
Has FT232 & regulator on the bottom, looks I made enough to put it on the top layer, will change that tomorrow to make assembly easier. Resonator & some caps under the 2560, will see if I can pull those to the top also. Change the resonator to an SMD crystal, add a couple of 22pF caps with it. Maybe change the regulator to something else, I don't really care for the 1117 type. Maybe add a 3.3V regulator also. Change the solder jumper to a couple of thru holes, add a DTR disable.
No ICSP header - gonna have to get by with a flying lead adapter from a programmer.
Big board: 5.5" x 0.9"
Not breadboard friendly tho, any more than my Mini2560 posted above is.
OOPS, overlooked that 
Got the USB connector and FT232 moved to the top layer last night, will make assembly easier. Working on adding pin names and replacing resonator with a crystal and caps next.
Also thinking to maybe just go with an FTDI Basic header, then folks can attach whatever USB/Serial module they want - and then unplug it if the module is to be embedded into something. That will make assembly real easy. Instead of the connector, FT232, numerous resistors, caps, and LEDs, would just have the FTDI Basic
($6.90 from www.tinyosshop.com with mini or micro USB connector types),
a 3.3V and 5V regulator, the power LED, and the 2560 and its components.
Switching to an FTDI header would be a good thing (if I were to embed the serial adapter, I'd use a CH340G, especially if I expected others to assemble it at home - SOIC-16 is much easier to handle, the chips are a tenth the cost, and they can be obtained without fear of their provenance, and, if I'm not mistaken, they require slightly fewer external components - 4 caps and a crystal.) - why force people to hold onto the baggage (in terms of power use, plus something being on those pins) of a serial adapter if their project doesn't need it?
Depending on what you're trying to accomplish, you might also look at the Teensy++ from PJRC.COM 128k flash, 8k RAM, native USB, 40 pin DIP format w 46 IOs, and still an AVR for good compatibility.
CrossRoads:
Ok, finally have a design I'm ready to go forward with. Any further thoughts?
I may have missed it but maybe have +5V going to a pin so an external 5 volt supply can be used to power the board.
Have a led on D13?
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Edit:
Some ccts. have a 22pF capacitor to ground on reset and a 1 meg across the crystal.
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VCC is on a couple external pins to power the '2560 and the 3.3V regulator from external 5V source.
There is not room to run 5V out to the suggested location. VCC from either USB or the 5V regulator is available on 2 pins next to that - I can bring VCC to one more pin as well.
Diode, I don't know - that only seems to be an issue when a mechanical switch is used. I have not come across Reset hanging when electrical reset is used. I'll see if I can fit one.
I'll see what I can do to get a signal from pin 20 out to an LED somewhere.
CrossRoads:
VCC is on a couple external pins to power the '2560 and the 3.3V regulator from external 5V source.
There is not room to run 5V out to the suggested location. VCC from either USB or the 5V regulator is available on 2 pins next to that - I can bring VCC to one more pin as well.
Diode, I don't know - that only seems to be an issue when a mechanical switch is used. I have not come across Reset hanging when electrical reset is used. I'll see if I can fit one.
I'll see what I can do to get a signal from pin 20 out to an LED somewhere.
I made an edit:
Some ccts. have a 22pF capacitor to ground on reset and a 1 meg across the crystal.
I've not had issues on boards using just the 10K pullup on Reset when a switch was not used. The cap is suggested for "noisy" environments. I don' add a switch on custom boards in general, I just wire one across the ICSP header if one is needed during code development. Which is next to never.
Resistor across the crystal, I've never done that either and have never had issues either. I'm not sure if there is room near the crystal to squeeze one in. I'll give it a shot. On the Mini2560, I didn't use one and that board has worked fine also.
Personally, I would have a 100nF from Reset to ground.
This would give power up delay for the controller and provide some noise immunity.
The diode would give a discharge path for the capacitor at power down.
Looks great!
If you add the D13 led, have optional trace cutting with header as in UNO.
Edit:
Are you still supplying ATMega1284P Duemilanova-style ?
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Yes, I'm still offering the ATMega1284P Duemilanova-style.
Assembled board & kit available.
Ok, here's the updated design.
Added an "L" LED.
Added solder jumpers to disconnect both L and PWR LED.
Added the Reset diode (but I don't plan to populate it).
Added the crystal resistor (but I don't plan to populate it).
Added solder jumpers to disable the LEDs, not enough room for male pin headers.
I'm still debating whether to change the Port names to Arduino names like so:
PE , // PE 0 ** 0 ** USART0_RX
PE , // PE 1 ** 1 ** USART0_TX
PE , // PE 4 ** 2 ** PWM2
PE , // PE 5 ** 3 ** PWM3
PG , // PG 5 ** 4 ** PWM4
PE , // PE 3 ** 5 ** PWM5
PH , // PH 3 ** 6 ** PWM6
PH , // PH 4 ** 7 ** PWM7
PH , // PH 5 ** 8 ** PWM8
PH , // PH 6 ** 9 ** PWM9
PB , // PB 4 ** 10 ** PWM10
PB , // PB 5 ** 11 ** PWM11
PB , // PB 6 ** 12 ** PWM12
PB , // PB 7 ** 13 ** PWM13
PJ , // PJ 1 ** 14 ** USART3_TX
PJ , // PJ 0 ** 15 ** USART3_RX
PH , // PH 1 ** 16 ** USART2_TX
PH , // PH 0 ** 17 ** USART2_RX
PD , // PD 3 ** 18 ** USART1_TX
PD , // PD 2 ** 19 ** USART1_RX
PD , // PD 1 ** 20 ** I2C_SDA
PD , // PD 0 ** 21 ** I2C_SCL
PA , // PA 0 ** 22 ** D22
PA , // PA 1 ** 23 ** D23
PA , // PA 2 ** 24 ** D24
PA , // PA 3 ** 25 ** D25
PA , // PA 4 ** 26 ** D26
PA , // PA 5 ** 27 ** D27
PA , // PA 6 ** 28 ** D28
PA , // PA 7 ** 29 ** D29
PC , // PC 7 ** 30 ** D30
PC , // PC 6 ** 31 ** D31
PC , // PC 5 ** 32 ** D32
PC , // PC 4 ** 33 ** D33
PC , // PC 3 ** 34 ** D34
PC , // PC 2 ** 35 ** D35
PC , // PC 1 ** 36 ** D36
PC , // PC 0 ** 37 ** D37
PD , // PD 7 ** 38 ** D38
PG , // PG 2 ** 39 ** D39
PG , // PG 1 ** 40 ** D40
PG , // PG 0 ** 41 ** D41
PL , // PL 7 ** 42 ** D42
PL , // PL 6 ** 43 ** D43
PL , // PL 5 ** 44 ** D44
PL , // PL 4 ** 45 ** D45
PL , // PL 3 ** 46 ** D46
PL , // PL 2 ** 47 ** D47
PL , // PL 1 ** 48 ** D48
PL , // PL 0 ** 49 ** D49
PB , // PB 3 ** 50 ** SPI_MISO
PB , // PB 2 ** 51 ** SPI_MOSI
PB , // PB 1 ** 52 ** SPI_SCK
PB , // PB 0 ** 53 ** SPI_SS
PF , // PF 0 ** 54 ** A0
PF , // PF 1 ** 55 ** A1
PF , // PF 2 ** 56 ** A2
PF , // PF 3 ** 57 ** A3
PF , // PF 4 ** 58 ** A4
PF , // PF 5 ** 59 ** A5
PF , // PF 6 ** 60 ** A6
PF , // PF 7 ** 61 ** A7
PK , // PK 0 ** 62 ** A8
PK , // PK 1 ** 63 ** A9
PK , // PK 2 ** 64 ** A10
PK , // PK 3 ** 65 ** A11
PK , // PK 4 ** 66 ** A12
PK , // PK 5 ** 67 ** A13
PK , // PK 6 ** 68 ** A14
PK , // PK 7 ** 69 ** A15
PJ , // PJ 2 ** 70 ** D70
PJ , // PJ 3 ** 71 ** D71
PJ , // PJ 4 ** 72 ** D72
PJ , // PJ 5 ** 73 ** D73
PJ , // PJ 6 ** 74 ** D74
PJ , // PJ 7 ** 75 ** D75
PH , // PH 2 ** 76 ** D76
PH , // PH 7 ** 77 ** D77
PG , // PG 3 ** 78 ** D78
PG , // PG 4 ** 79 ** D79
PE , // PE 2 ** 80 ** D80
PE , // PE 6 ** 81 ** D81
PE , // PE 7 ** 82 ** D82
PD , // PD 4 ** 83 ** D83
PD , // PD 5 ** 84 ** D84
PD , // PD 6 ** 85 ** D85
D70 to D85 are the pins that a Mega doesn't bring out.
Do you think you might need a 100nF capacitor on the input of the 5 volt regualtor?
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