"I'd like to design a new development board with a 8051 microcontroller's familly for general purpose."
That seems like reinventing the wheel, there are hundereds already available.

"Moreover, I absolutely want to use the ISP capability instead of classsic EPROM."
If you are thinking of the uC 'built in' ISP, see below

"It seems to me that a minimum of 8Kb of RAM would be enough to manage all the variables."
P89C668 from Philips, ISP, 64k Flash, 8k RAM

"Do you think I should design a board with external RAM & FLASH."
Then you would not have the uC ISP

Erik