Nor is there some setting on a QTableWidgetItem or the underlying setItem(index, value, some-role) to control padding. Padding is just a paint area feature.

So, yes, you do need to write a delegate and attach it to your table. Although they seem intimidating initially they are actually very simple once you use them.

Here is complete PyQt6 program showing what you are wanting to achieve:

import sys
from PyQt6.QtWidgets import (
    QApplication, QStyledItemDelegate, QStyleOptionViewItem, QTableWidget, QTableWidgetItem)
from PyQt6.QtGui import QColor
from PyQt6.QtCore import Qt

class TableDelegate(QStyledItemDelegate):
    def paint(self, painter, option, index):
        option = QStyleOptionViewItem(option)

        # for all cells/items *other than* those in column 0
        # adjust the rectangle to draw/paint in for the padding at each side
        if index.column() != 0:
            option.rect.adjust(10, 5, -10, -5)

        # Visualise the actual non-padded area, just so you can see what the effect is
        painter.save()
        painter.fillRect(option.rect, QColor(255, 255, 0, 120))
        painter.restore()

        # allow the cell to be painted, with its rectangle having been potentially changed above
        super().paint(painter, option, index)


if __name__ == "__main__":
    app = QApplication(sys.argv)
    tw = QTableWidget(5, 5)
    for row in range(5):
        for col in range(5):
            tw.setItem(row, col, QTableWidgetItem("Hello"))
    # Create an instance of your delegate class and attach it to the table widget
    tw.setItemDelegate(TableDelegate())
    tw.show()
    sys.exit(app.exec())

If it helps: you can first fill the whole of the rectangle fillRect(option.rect) to get a background color on the rectangle passed in and then call option.rect.adjust() to reduce the rectangle for the padding. If that is what you wanting to achieve? Just change the order:

painter.fillRect(option.rect, QColor(255, 255, 0, 120))
option.rect.adjust(10, 5, -10, -5)
super().paint(painter, option, index)

If you know you want it to apply/not apply to a given column where you know the column number (e.g. your "2nd column cells") it already does that. If you are asking for some reason if you can examine the cell content dynamically at runtime (e.g. for "text" or "empty" etc.) then, yes, we can make it do that, but is that what you really mean? Otherwise you would have to spell out just what you intend.

Nor is there some setting on a QTableWidgetItem or the underlying setItem(index, value, some-role) to control padding. Padding is just a paint area feature.

So, yes, you do need to write a delegate and attach it to your table. Although they seem intimidating initially they are actually very simple once you use them.

Here is complete PyQt6 program showing what you are wanting to achieve:

import sys
from PyQt6.QtWidgets import (
    QApplication, QStyledItemDelegate, QStyleOptionViewItem, QTableWidget, QTableWidgetItem)
from PyQt6.QtGui import QColor
from PyQt6.QtCore import Qt

class TableDelegate(QStyledItemDelegate):
    def paint(self, painter, option, index):
        option = QStyleOptionViewItem(option)

        # for all cells/items *other than* those in column 0
        # adjust the rectangle to draw/paint in for the padding at each side
        if index.column() != 0:
            option.rect.adjust(10, 5, -10, -5)

        # Visualise the actual non-padded area, just so you can see what the effect is
        painter.save()
        painter.fillRect(option.rect, QColor(255, 255, 0, 120))
        painter.restore()

        # allow the cell to be painted, with its rectangle having been potentially changed above
        super().paint(painter, option, index)


if __name__ == "__main__":
    app = QApplication(sys.argv)
    tw = QTableWidget(5, 5)
    for row in range(5):
        for col in range(5):
            tw.setItem(row, col, QTableWidgetItem("Hello"))
    # Create an instance of your delegate class and attach it to the table widget
    tw.setItemDelegate(TableDelegate())
    tw.show()
    sys.exit(app.exec())